Profile photo of David Mitchell, PhD.

David Mitchell, PhD.

Chemistry leadership for pharmaceutical drug design, development and manufacturing.
Certificate # 971
DMIT Consulting Services, LLC
382 NE 191ST ST; #66831
Miami, FL 33179
Phone #: 317-794-4260
Cell #: 317-794-4260

DMIT Consulting Services, LLC, provides expertise leadership to the pharmaceutical, biotechnology and chemical industries. Primary focus is drug product synthesis design, development and optimization from discovery milligram lead to multi-ton commercial manufacturing.

Industrial Experience:

DMIT Consulting Services, LLC; Naples, Florida. Established 2018, Principal

Eli Lilly and Company, Indianapolis, IN.  Small Molecules Design and Development.  Research Advisor (2004 – 2017); Senior Research Scientist (1998-2004), Research Scientist (1994-1998), Senior Organic Chemist (1989-1994). Primary duties include the design and development of synthesis methodology for pharmaceutical products from discovery to commercial manufacturing. (28 years)

Procter and Gamble Company, Miami Valley, Ohio. Summer Intern. Assisted in the improvement of the potato chip flavor of a particular salted snack.  Summer Intern, 1984. (10 weeks)

Burroughs Wellcome Company, Research Triangle Park, NC.  Summer Intern. Design new method in the multigram synthesis of a drug to be used in early phase clinical trials.  Summer Intern, 1983. (10 weeks)

Hess Oil Company, St. Croix, US Virgin Islands. Quality Control Laboratory. Apprentice. Responsibilities included the application of basic qualitative tests used in oil refinery.  CoOp and Summer Intern, 1980. (2 years)

Specializing In:

Specific services provided include the following categories:

1)  Pharmaceutical project management leadership

2)  API evaluation, practical design, development and optimization

3)  CM&C program leadership and regulatory affairs

4)  Medicinal chemistry and process chemistry SAR development interface

5) Process chemistry synthesis design, development and optimization stewardship

6)  Synthesis interface with engineering, analytical chemistry and manufacturing

7) Regulatory oversight with IND, NDA (FDA, EMA and global regulatory agencies)

8)  CMO selection, relationship oversight and general management

9)  Due diligence for partnering or acquisition of pharmaceutical products

10) Academic, government and professional societies scientific collaboration

11)  Expert witness for litigation in the legal profession

Society Memberships:

American Chemical Society
Chemical Consultants Network

Patents and Publications:

19] US7034045 B1, Bender, D. M., Cantrell, B.E., Fray, A. H, Jones, W. D., Miller, W. D, Mitchell, D., Simon, R. L., Zarrinmayeh, H., Zimmerman, D. M.; Monofluoroalkyl Derivatives, April 26, 2006.
18] EP1353910A2, Koenig, Thomas; Audia, James; Mitchell, David; Mcdaniel, Stacey; Lactam Compounds, October 22, 2003.
17] EP1345955, Koenig, T. M.; Mitchell, D.; Nissen, J. S. Lactam Dipeptide and its use in Inhibiting Beta-Amyloid Peptide, September 24, 2003.
16] WO 0240508 A2, Koenig, Thomas; Mitchell, David; Nissen, Jeffrey; Lactam Compounds, May, 2002.
15] WO0240451 A2, Koenig, Thomas; Audia, James; Mitchell, David; McDaniel, Stacey; Buccilli; Lynne; Engel, Gary; Nissen, Aikins, James; Lactam Compounds, May, 2002.
14] EP1183232, Bender, D. M.; Cantrell, B. E.; Fray, A. H.; Jones, W. D.; Miller, W. D.; Mitchell, D.; Simon, R, L.; Zarrinmayeh, H.; Zimmerman, D., Monofluoroalkyl Derivatives, March 6, 2002.
13] WO0068182, Brennan, J.; Diseroad, W.; Hay, L.; Mitchell, D.; Process for Crystallizing (R) Fluoxetine Hydrochloride, November 16, 2000.
12] WO0066546, Bender, D. M.; Cantrell, B. E.; Fray, A. H.; Jones, W. D.; Miller, W. D.; Mitchell, D.; Simon, R, L.; Zarrinmayeh, H.; Zimmerman, D., Monofluoroalkyl Derivatives, November 9, 2000.
11] WO0064855; Koenig, Thomas; Mitchell, David; Epimerization Reaction for the Production of R-Fluoxetine, November 2, 2002.
10] US06,069,247, Lynne A. Hay, David Mitchell, Eli Lilly and Company, Process for Preparing Substituted Acrylamides. 2000.
9] EP0944581A1, Hay, Lynne; Mitchell, David; Process for Preparing Substituted Acrylamides, September 29, 1999.
8] US05,917,038A1, Lynne A. Hay, David Mitchell, Eli Lilly and Company, Process for Preparing Substituted Acrylamides. June 29, 1999.
7] WO9822429A1, Hay, Lynne; Mitchell, David; Process for Preparing Substituted Acrylamides, May 28, 1998.
6] US005250571, Ray W. Fuller, David Mitchell, David W. Robertson, Gregory A. Stephenson, David Wong, Eli Lilly and Company, (S)-Norfluoxetine in Method of Inhibiting Serotonin Uptake, September 5,1993.
5] JP05092946A, David Mitchell, Eli Lilly and Company, Regioselective Synthesis, April 16, 1993.
4] JP05078302A, David Mitchell, Eli Lilly and Company, Synthesis of B-Cyanohydrin, March 30, 1993.
3] US005136079A, David Mitchell, Eli Lilly and Company, Regioselective Synthesis, 1992.
2] US005136078A, David Mitchell, Eli Lilly and Company, Synthesis of B-Cyano-hydrin, 1992
1] EP 444855 A1 19910904. Fuller, Ray Ward; Mitchell, David; Robertson, David Wayne; Stephenson, Gregory Alan; Wong, David Taiwai. Novel crystalline forms of (S)-norfluoxetine hydrochloride, February 26, 1991.
49] Lu, Y.; Cole, K. P.; Fennell, J. W.; Maloney, T. D.; Mitchell, D.; Subbiah, R.; Ramadas, B. “An Alternative Indazole Synthesis for Merestinib.” Org. Process Res. Dev. 2018, 22 (3), 409-419.
48] Mitchell, D. “Synthesis of LY2623091. Highlights in Chemical Synthesis.” Synfacts, 2017, 13, 449-562.
47] Hansen, M. M.; Kallman, N. J.; Koenig, T. M.; Linder, R. J.; Richey, R. N.; Rizzo, J. R.; Ward, J. A.; Yu, H.; Zhang, T. Y.; Mitchell, D. “An Efficient Synthesis Process for MR Antagonist LY2623091.” Org. Process Res. Dev. 2017, 21(2), 208-217.
46] Risley, D. S.; Chaddha, R.; Mitchell, D. “Retention, direct detection, and quantitation of palladium (II) using high-performance liquid chromatography and evaporative light scattering detection.” J. Liq. Chromatogr. Related. Technol. 2017, accepted version posted on line August 4, (DOI: 10.1080/10826076.2017.1360907).
45] Cole, K. P.; Groh, J. M.; Johnson, M. D.; Burcham, C. L.; Campbell, B. M.; Diseroad, W. D.; Heller, M. R.; Howell, J. R.; Kallman, N. J.; Koenig, T. M.; May, S. A; Miller, R. D.; Mitchell, D.; Myers, D. P.; Myers, S. S.; Phillips, J. P.; Polster, C. S.; White, T. D.; Cashman, J.; Hurley, D.; Moylan, R.; Sheehan, P.; Spencer, R. D.; Desmond, K.; Desmond, P.; Gowran, O. “Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow
CGMP conditions.” Science, 2017, 356(6343), 1144-1150.
44] Sharif, S.; Day, J.; Hunter, H. N.; Lu, Y.; Mitchell, D.; Rodriguez, M. J.; Organ, M. G. “Cross-coupling of primary amides to aryl- and heteroaryl-partners using (DiMeIHeptCl)Pd promoted by trialkylboranes or BCF.” J. Am. Chem. Soc. 2017, ASAP (Web 16 Oct 2017).
43] Khadra, A.; Mayer, S.; Mitchell, D.; Rodriguez, M. J.; Organ, M. G. “A General Protocol for the Broad-Spectrum Cross-Coupling of Nonactivated Sterically Hindered 1° and 2° Amines.” Organometallics 2017, 36(17), 3365-3370.
42] Lombardi, C.; Mitchell, D.; Rodriguez, M. J.; Organ, M. G. “Pd-PEPPSI-IPentCl-Catalyzed Amination Using Aminotriphenylsilane as an Ammonia Surrogate.” European Journal of Organic Chemistry, 2017, 11, 1510-1513.
41] Lombardi, C.; Day, J.; Chandrasoma, N.; Mitchell, D.; Rodriguez, M. J.; Farmer, J. L.; Organ, M. G. “Selective Cross-Coupling of (Hetero)aryl Halides with Ammonia To Produce Primary Arylamines using Pd-NHC Complexes.” Organometallics, 2017, 36(2), 251-254.
40] Organ, M. G.; Sharif, S.; Mitchell, D.; Rodriguez, M.; Farmer, J. L. A. “N-Heteroarylation of Optically Pure α-Amino Esters using the Pd-PEPPSI-IPentCl-o-picoline Pre-catalyst.” Chemistry – A European Journal 2016, 22(42), 14860-14863.
39] Organ, M. G.; Atwater, B.; Rodriguez, M. J.; Chandrasoma, N.; Mitchell, D. “Pd-PEPPSI-IHeptCl: A General Purpose, Highly Reactive Catalyst for the Selective Coupling of Secondary Alkyl Organozincs.” Chemistry – A European Journal, 2016, 22(41), 14531-14534.
38] Kallman, N. J.; Cole, K. P.; Koenig, T. M.; Buser, J. Y.; McFarland, A. D.; McNulty, L. M.; Mitchell, D. “Synthesis of Aminopyrazoles from Isoxazoles: Comparison of Preparative
Methods by in situ NMR Analysis.” Synthesis, 2016, 48, 3537-3543.
37] Cole, K. P.; Campbell, B. M.; Forst, M. B.; McClary G. J.; Hess, M.; Johnson, M. D.; Miller, R. D.; Mitchell, D.; Polster, C. S.; Reizman, B. “An Automated Intermittent Flow Approach to Continuous Suzuki Coupling.” Org. Process Res. Dev. 2016, 20(4), 820-830.
36] Sharif, S.; Rucker, R. P.; Chandrasoma, N.; Mitchell, D.; Rodriguez, M. J.; Froese, R. D. J.; Organ, M. G. “Selective Monoarylation of Primary Amines Using the Pd-PEPPSI-IPent(Cl) Precatalyst.” Angew. Chem. Int. Ed. 2015, 54 (33), 9507-9511.
35] Atwater, B.; Chandrasoma, N.; Mitchell, D.; Rodriguez, M. J.; Pompeo, M.; Froese, R. D. J.; Organ, M. G. “The Selective Cross-Coupling of Secondary Alkyl Zinc Reagents to Five-Membered-Ring Heterocycles Using Pd-PEPPSI-IHept(Cl).” Angew. Chem. Int. Ed. 2015, 54 (33), 9502-9506.
34] Deasy, R. E.; Slattery, C. N.; Kissane, M.; McNamara, O. A.; Lynch, D.; Maguire, A. R.; Moynihan, H. A.; O’Keeffe, S.; Kopach, M. E.; Mitchell, D.; Magnus, N. A.; Kjell, D. P.; Moher, E. D. “Leveraging an Industrial-Academic Partnership To Optimize Small Molecule Process Development within the Pharmaceutical Industry.” Org. Process Res. Dev. 2015, 19 (2), 344-346.
33] Mitchell, D.; Luo, Y.; McNulty, L. M.; Buser, J. Y.; McFarland, A. D. “A Convenient and Practical Synthesis of Aminopyrazole.” Synthesis, 2015, 47, 235-241.
32] Ritter, S. K. interview with D. Mitchell. “Living Up to the Process Challenge.” Chem. Eng. News. 2014, 93(12), 30-33.
31] Grainger, D. M.; Zanotti-Gerosa, A.; Cole, K. P.; Mitchell, D.; May, S. A.; Pollock, P. M.; Calvin, J. R. “Development of a Stepwise Reductive Deoxygenation Process by Ru-Catalyzed Homogeneous Ketone Reduction and Pd-Catalysed Hydrogenolysis in the Presence of Cu Salts.” ChemCatChem. 2013, 5, 1205-1210.
30] Campbell, A. N.; Cole, K. P.; Martinelli, J. R.; May, S. A.; Mitchell, D.; Pollock, P. M.; Sullivan, K. A. “Development of an Alternate Synthesis for a Key JAK2 Inhibitor Intermediate via Sequential C-H Bond Functionalization.” Org. Process Res. Dev. 2013, 17(2), 273-281.
29] Kissane, M.; McNamara, O. A.; Mitchell, D.; Coppert, D. M.; Humphrey, M. A.; Lorentz, K. T.; Maguire, A. R. “Expanded scope of heterocyclic biaryl synthesis via a palladium-catalysed thermal decarboxylative cross-coupling reaction.” Tetrahedron Lett. 2012, 53 (4), 403-405.
28] Mitchell, D.; Cole, K. P.; Pollock, P. M.; Coppert, D. M.; Burkholder; T. P.; Clayton, J. R. “Development and a practical Synthesis of the JAK2 Inhibitor LY2784544.” Org. Process Res. Dev. 2012, 16 (1), 70-81.
27] Mitchell, D.; Coppert, D.; Moynihan, H. A.; Lorenz, K. T; Kissane, M.; McNamera, O. A.; Maguire, A. R. “A Practical Synthesis of Biaryls via a Thermal Decarboxylative Pd-Catalyzed Cross-Coupling Reaction Operating at Moderate Temperature.” Org. Process Res. Dev. 2011, 15, 981-985.
26] Halford, B. (with Mitchell, D.) “From a Teaspoon to a Ton,” Chem. Eng. News. 2010, 88(36), 17-28.
25] Cole, K. P.; Mitchell, D. Carr, M. A.; Stout, J. R; Belvo, M. D. “Synthesis and axial chirality of an enantiopure aminodibenzazepinone.” Tetrahedron: Asymmetry, 2009, 20(11), 1262-1266.
24] Boini, S. K.; Vaid R. K.; Mitchell, D.; Moder, K. P. “Synthesis of a substituted benzazepin-2-one dehydrate.” Synthesis, 2009, 12, 1983-1986.
23] Yates, M. H.; Koenig, T. M.; Kallman, N. J.; Ley, C. P.; Mitchell, D. “An Efficient Synthesis of a Multipotent Eicosanoid Pathway Modulator.” Org. Process Res. Dev. 2009, 13(2), 268-275.
22] Pu, Y. J.; Vaid, R. K.; Boini, S. K.; Towsley, R. W.; Doecke, C. W.; Mitchell, D. “A practical method for functionalized peptide or amide bond formation in aqueous-ethanol media with EDC as activator.” Org. Process Res. Dev. 2009, 13(2), 310-314.
21] Xie, C.; Sullivan, K.; Pu, J.; Mitchell, D. “Selective Monoarylation of Benzenediols via Dianion Intermediates.” Syn. Comm. 2008, 38, 21-32.
20] Zhang, F.; Mitchell, D.; Pollock, P.; Zhang, T. “Efficient synthesis of 3-oxygenated benzothiophene derivatives.” Tetrahedron Lett. 2007, 48, 2349-2352.
19] Yu, Y.; Stephenson, G. A.; Mitchell, D. “Benzoazepinone Synthesis: Seven Membered Ring Formation by Palladium-Catalyzed Cyclization of Alkynyl Benzeneacetamides.” Tetrahedron. Lett. 2006, 47, 3811-3814.
18] Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y. “Practical Method for Transforming Alkynes into -Diketones.” J. Org. Chem. 2006, 71(2), 826-828.
17] Mitchell, D.; Audia, J. A.; Buccilli, L. A.; Koenig, T. M.; McDaniel, S, L.; Nissen, J. S. “Dynamic and Chemical Resolution of Aminobenzoazepinone.” Tetrahedron: Asymmetry, 2005, 16, 3814-3819.
16] Mitchell, D.; Yu, H. “Synthetic Application of Palladium-Catalyzed Hydroarylation and Related Systems” Current Opinion in Drug Discovery and Development, 2003, 6(6), 876-883.
15] Wan, Z.; Jones, D. C; Koenig, T. M.; Pu, Y. J.; Mitchell, D.; “Vinyl Aryl Ethers from Copper-Catalyzed Coupling of Vinyl Halides and Phenols.” Tetrahedron Lett. 2003, 44, 8257-8259.
14] Godfrey, A. G.; Brooks, D. A.; McCarthy, J.; Hay, L. A.; Wepsiec, J.; Peters, M.; Mitchell, D. “Application of the Dakin-West Reaction for the Synthesis of Oxazole-Containing Dual PPAR a/g agonist.” J. Org. Chem. 2003, 68, 2623-2632.
13] Robbins, D. K.; Dodson, P. N.; Buccilli, L. A.; Mitchell, D. “Utilizing Capillary Gas Chromatography Mass Spectrometry to Determine 4-Benzotrifluoride t-Butyl Ether as a Reaction By-Product in Fluoxetine Synthesized using Potassium t-Butoxide as Base.” J. Pharm. Biomed. Anal. 2003, 31(1), 63-74.
12] Mitchell, D. “ From Bench Top Research to Pilot-Plant Production and Process Research in the Pharmaceutical Industry.” (ACS Volume, Book Chapter). September 15, 2000.
11] Hay, L. A.; Koenig, T. M.; Ginah, F. O.; Copp, J. D.; Mitchell, D. “Palladium-Catalyzed Hydroarylation of Propiolamides. A Regio- and Stereocontrolled Method for Preparing 3,3-Diaryl Acrylamides.” J. Org. Chem. 1998, 63, 15, 5050-5058.
10] Hay, L. A.; Mitchell, D. “A Regio- and Stereocontrolled Method for Preparing 3,3-Diaryl Acrylamides.” Tetrahedron Lett. 1997, 38, 6533-6536.
9] Huff, B. E.; Koenig, T. M.; Mitchell, D.; Staszak, M. A. “Synthesis of Unsymmetrical Biaryls Using a Modified Suzuki Cross-Coupling: 4-Biphenylcarbox-aldehyde ([1,1’-Biphenyl]-4-Carboxaldehyde).” Organic Syntheses, 1997, 75, 53-60.
8] Mitchell, D.; Doecke, C. W.; Hay, L. A.; Koenig, T. M.; Wirth, D. D. “Ortho-Hydroxyl Assisted Deoxygenation of Phenones. Regiochemical Control in the Synthesis of Monoprotected Resorcinol and Related Systems.” Tetrahedron Lett. 1995, 36(30), 5335-5338.
7] Mitchell, D.; Koenig, T. M. “Synthesis of R- and S- Fluoxetine, Norfluoxetine and Related Compounds from Styrene Oxide.” Synthetic Commun. 1995, 25(8), 1231-1238.
6] T. M. Koenig and D. Mitchell, “A Convenient Method for Preparing Enantiomerically Pure Norfluoxetine, Fluoxetine and Tomoxetine.” Tetrahedron Lett. 1994, 35(9), 1339-1342.
5] Mitchell, D.; Koenig, T. M. “Regiospecific Opening of 1,2 Epoxides with Acetone Cyanohydrin under Mildly Basic Conditions.” Tetrahedron Lett. 1992, 33(23), 3281-3284.
4] Mitchell, D.; Liebeskind, L. S. “Benzoabikoviromycin, a Potential Antiviral Agent Synthesized by the Palladium-Catalyzed Ring Expansion of 2-Alkynyl-2-hydroxybenzocyclobutenones.” J. Am. Chem. Soc. 1990, 112(1), 291-296.
3] Mitchell, D. “Transition Metal Organometallics in the Synthesis of Biologically Active Molecules: Alkylidene Indianones and Quinines.” Ph.D. Thesis, Emory University, Atlanta, GA, Advisor: Lanny S. Liebeskind, 1989.
2] Liebeskind, L. S.; Chidambaram, R.; Mitchell, D.; Foster, B. “Metal Mediated Route to 5-Membered Rings.” Pure and Applied Chemistry 1988, 60(1), 27-34.
1] Liebeskind, L. S.; Mitchell, D.; Foster, B. “A Stereoselective Palladium
Catalyzed Route to 4-Oxygenated 5-Alkylidene Cyclopentadienes and 3-Oxygenated-2-Alkylidene Indenones.” J. Am. Chem. Soc. 1987, 109(25), 7908-7910.