Acetic Acid → HCID 86698049, compound

HRID 518897Notes

Reaction equation

HRID 518897 reaction equation
C(O)(=O)C.[O:5]1[CH2:8][C:7](=O)[CH2:6]1.C([BH3-])#N.[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]2[CH:23]=[C:22]([NH:24][C:25]3[N:26]=[CH:27][C:28]4[S:33][C:32]([C:34]([NH2:36])=[O:35])=[C:31]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=5[O:43][C:44]([F:47])([F:46])[F:45])[C:29]=4[N:30]=3)[N:21]([CH:48]([CH3:50])[CH3:49])[N:20]=2)[CH2:15][CH2:14]1>C1COCC1>[O:5]1[CH2:6][CH:7]([N:13]2[CH2:14][CH2:15][CH:16]([C:19]3[CH:23]=[C:22]([NH:24][C:25]4[N:26]=[CH:27][C:28]5[S:33][C:32]([C:34]([NH2:36])=[O:35])=[C:31]([C:37]6[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=6[O:43][C:44]([F:45])([F:46])[F:47])[C:29]=5[N:30]=4)[N:21]([CH:48]([CH3:50])[CH3:49])[N:20]=3)[CH2:17][CH2:18]2)[CH2:8]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 498716Cyano-borohydride3×HCID 150242543-Oxetanone3×HCID 86698047HCID 86698047, compound

Product 1

HCID 86698049HCID 86698049, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1 ml of acetic acid, 6 microliters of 3-oxetanone and 190 mg of amberlite resin IRA400 cyanoborohydride (Aldrich, loading 2×10−3 mol/g) are added, at ambient temperature, to a solution of 50 mg of 2-{[3-(piperidin-4-yl)-1-(propan-2-yl)-1H-pyrazol-5-yl]amino}-7-[2-(trifluoromethoxy)phenyl]thieno[3,2-d]pyrimidine-6-carboxamide in 3 ml of anhydrous THF, under an argon atmosphere. After stirring for 4 h at ambient temperature, 10 microliters of 3-oxetanone and 186 mg of the same amberlite resin IRA400 cyanoborohydride are added and the mixture is left to stir for a further 15 h. A further 6 microliters of 3-oxetanone and 100 mg of amberlite resin IRA400 cyanoborohydride are added and the mixture is then left to stir for 2 h. The mixture is filtered and the resin is washed with 50 ml of ethyl acetate then 20 ml of ethanol. The filtrate is concentrated under vacuum and the crude product is purified by flash chromatography on silica gel, elution being carried out with a dichloromethane/methanol/NH4OH (96/4/0.1%) mixture, so as to obtain 30 mg of 2-({3-[1-(oxetan-3-yl)piperidin-4-yl]-1-(propan-2-yl)-1H-pyrazol-5-yl}amino)-7-[2-(trifluoromethoxy)phenyl]thieno[3,2-d]pyrimidine-6-carboxamide in the form of a yellow solid.

Workup

  1. waitthe mixture is left
  2. stirringto stir for a further 15 h
  3. waitthe mixture is then left
  4. stirringto stir for 2 h
  5. filtrationThe mixture is filtered
  6. washthe resin is washed with 50 ml of ethyl acetate
  7. concentrationThe filtrate is concentrated under vacuum
  8. customthe crude product is purified by flash chromatography on silica gel, elution

Sources & evidence

ORD record
ord-400c7b9c27014a4dbc77005c96647930
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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