Trifluoroacetic acid → [6-Fluoro-5-(7H-pyrrolo[2,3-d]pyrimidin-5-ylmethyl)-pyridin-2-yl]-(4-methoxy-benzyl)-amine

HRID 1775184Notes

Reaction equation

C(OC(=O)[N:7]([C:17]1[CH:22]=[CH:21][C:20]([CH:23](O)[C:24]2[C:32]3[CH:31]=[N:30][CH:29]=[N:28][C:27]=3[N:26]([Si](C(C)C)(C(C)C)C(C)C)[CH:25]=2)=[C:19]([F:44])[N:18]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=1)(C)(C)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[F:44][C:19]1[N:18]=[C:17]([NH:7][CH2:8][C:9]2[CH:10]=[CH:11][C:12]([O:15][CH3:16])=[CH:13][CH:14]=2)[CH:22]=[CH:21][C:20]=1[CH2:23][C:24]1[C:32]2[CH:31]=[N:30][CH:29]=[N:28][C:27]=2[NH:26][CH:25]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To {6-fluoro-5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-pyridin-2-yl}-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (67, 27 g, 42.5 mmol) in 700 mL of acetonitrile, triethylsilane (67.8 mL, 425 mmol) and trifluoroacetic acid (32.7 mL, 425 mmol) were added. The reaction was stirred at 50° C. overnight, solvents removed under vacuum, and the residue taken up in ethyl acetate and poured into aqueous potassium carbonate. The organic layer was separated, concentrated under vacuum and purified by silica gel column chromatography, eluting with 0-10% methanol in dichloromethane. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (P-0105, 4.5 g, 12.38 mmol, 29.2% yield).

Workup

customsolvents removed under vacuum
additionpoured into aqueous potassium carbonate
customThe organic layer was separated
concentrationconcentrated under vacuum
custompurified by silica gel column chromatography
washeluting with 0-10% methanol in dichloromethane
customthe solvents removed under vacuum

Sources & evidence

ORD record: ord-f67bce324ae1481fb9c3bc5e3a93b750
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260437B2

Reaction notes

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