Acetic Acid → HCID 178488239, compound

HRID 898047Notes

Reaction equation

HRID 898047 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH2:7][C:8]1[N:13]=[CH:12][N:11]=[C:10]2[N:14]([CH:39]3[CH2:44][CH2:43][C:42](=O)[CH2:41][CH2:40]3)[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:36])[C:25]4[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:26]=4[F:35])=[C:19]([O:37][CH3:38])[CH:18]=3)[C:9]=12.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C.O>[NH2:7][C:8]1[N:13]=[CH:12][N:11]=[C:10]2[N:14]([C@H:39]3[CH2:44][CH2:43][C@@H:42]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[CH2:41][CH2:40]3)[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:36])[C:25]4[CH:30]=[CH:29][C:28]([C:31]([F:33])([F:34])[F:32])=[CH:27][C:26]=4[F:35])=[C:19]([O:37][CH3:38])[CH:18]=3)[C:9]=12.[NH2:7][C:8]1[N:13]=[CH:12][N:11]=[C:10]2[N:14]([C@H:39]3[CH2:44][CH2:43][C@H:42]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[CH2:41][CH2:40]3)[N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:36])[C:25]4[CH:30]=[CH:29][C:28]([C:31]([F:33])([F:34])[F:32])=[CH:27][C:26]=4[F:35])=[C:19]([O:37][CH3:38])[CH:18]=3)[C:9]=12

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 22347075HCID 22347075, compound

Product 2

HCID 178488239HCID 178488239, compoundHCID 178488240HCID 178488240, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

Morpholine (0.08 mL, 0.93 mmol) was added into a mixture of N1-{4-[4-amino-1-(4-oxocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-trifluoromethylbenzamide (0.42 g, 0.78 mmol) and acetic acid (0.11 mL, 1.86 mmol) in dichloroethane (25 mL). The mixture was stirred at ambient temperature for 10 minutes. Sodium triacetoxyborohydride (0.23 g, 1.09 mmol) was added and the mixture was stirred at ambient temperature overnight. Water (6 mL) was added followed by sodium bicarbonate (0.38 g, 4.53 mmol). The mixture was stirred for 1 hour and the organic layer was separated. The aqueous layer was extracted with dichloromethane (20 mL). The combine organics were dried over magnesium sulfate, filtered and evaporated under reduced pressure to give a crude product. The crude product was purified by flash column chromatography on silica using Isco system to provide cis-N1-{4-[4-amino-1-(4-morpholinocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-trifluoromethylbenzamide (0.23 g, 0.37 mmol) and trans-N1-{4-[4-amino-1-(4-morpholinocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-trifluoromethylbenzamide (0.09 g, 0.14 mmol) as white solids.

Workup

  1. stirringthe mixture was stirred at ambient temperature overnight
  2. stirringThe mixture was stirred for 1 hour
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with dichloromethane (20 mL)
  5. dry with materialThe combine organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customto give a crude product
  9. customThe crude product was purified by flash column chromatography on silica using Isco system

Sources & evidence

ORD record
ord-0473bb52a11e4ecc9528fab6bf0d5780
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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