Isonicotinic Acid → HCID 73426060, compound

HRID 1507584Notes

Reaction equation

[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[NH2:17][C:18]1[C:26]([F:27])=[C:25]2[C:21]([C:22]([CH3:31])([CH3:30])[C:23](=[O:29])[N:24]2[CH3:28])=[CH:20][C:19]=1[F:32]>CN(C=O)C.C([O-])(O)=O.[Na+]>[F:32][C:19]1[CH:20]=[C:21]2[C:25](=[C:26]([F:27])[C:18]=1[NH:17][C:1](=[O:9])[C:2]1[CH:3]=[CH:4][N:5]=[CH:6][CH:7]=1)[N:24]([CH3:28])[C:23](=[O:29])[C:22]2([CH3:31])[CH3:30]

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of isonicotinic acid (70 mg, 0.569 mmol) in DMF (2 ml) were added triethylamine (0.24 ml, 1.7 mmol) and Mukaiyama reagent (312 mg, 1.13 mmol) followed by the addition of 6-amino-5,7-difluoro-1,3,3-trimethyl-1,3-dihydro-indol-2-one (154 mg, 0.682 mmol). The resultant reaction mixture was stirred at 25° C. for 12 hours. The mixture was diluted with saturated aqueous NaHCO3 solution (10 ml), and extracted with dichloromethane (2×20 ml). The combined organic layers were washed with brine (15 ml), dried over anhydrous Na2SO4 and the solvent was evaporated. The crude material was purified by column chromatography with amine functionalized silica gel using ethyl acetate/heptane as eluent, followed by purification by prep-HPLC. The title compound was obtained as off-white solid (45 mg).

Workup

customThe resultant reaction mixture
extractionextracted with dichloromethane (2×20 ml)
washThe combined organic layers were washed with brine (15 ml)
dry with materialdried over anhydrous Na2SO4
customthe solvent was evaporated
customThe crude material was purified by column chromatography with amine functionalized silica gel
customfollowed by purification by prep-HPLC

Sources & evidence

ORD record: ord-5ff1fb3381ef4281a11135dda4cbaa0b
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221816B2

Reaction notes

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