HCID 7021725, compound → HCID 20817157, compound

HRID 432485Notes

Reaction equation

HRID 432485 reaction equation
[C:1]1([C@H:7]([CH3:12])[CH2:8][C:9](Cl)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][C:14]1[N:19]=[CH:18][N:17]=[C:16]2[N:20]([CH:32]3[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]3)[N:21]=[C:22]([C:23]3[CH:28]=[CH:27][C:26]([NH2:29])=[C:25]([O:30][CH3:31])[CH:24]=3)[C:15]=12>ClCCl.N1C=CC=CC=1>[NH2:13][C:14]1[N:19]=[CH:18][N:17]=[C:16]2[N:20]([CH:32]3[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]3)[N:21]=[C:22]([C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:9](=[O:10])[CH2:8][C@H:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH3:12])=[C:25]([O:30][CH3:31])[CH:24]=3)[C:15]=12

Participants

5

Reactant 2

HCID 7021725HCID 7021725, compoundHCID 22347344HCID 22347344, compound

Product 1

HCID 20817157HCID 20817157, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

(3R)-3-Phenylbutanoyl chloride (2.22 g, 12.18 mmol) in dichloromethane (10 mL) was added to a solution of 4-[4-amino-3-(4-amino-3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-cyclohexanone (2.86 g, 8.12 mmol) in pyridine (50 mL) at −10° C. After 15 minutes, the ice-water bath was removed and the reaction mixture was stirred at room temperature overnight. Sodium hydroxide (1.0N, 15 mL) was added and the organic solvent was evaporated. The aqueous residue was extracted with dichloromethane. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichlromethane/methanol (95:5) as mobile phase to give N1-{4-[4-amino-1-(4-oxocyclohexyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-(3R)-3-phenylbutanamide (3.11 g, 77%). 1H NMR (CDCl3) δ 1.40 (d, J=6.97 Hz, 3H), 2.04 (m, 1H), 2.59-2.78 (m, 9H), 3.40 (m, 1H), 3.98 (s, 3H), 5.28 (m, 1H), 5.70 (bs, 2H), 7.15-7.35 (m, 7H), 7.66 (s, 1H), 8.38 (s, 1H), 8.51 (d, J=8.18, 1H). HPLC (Waters Alliance-Column: Waters SymmetryShield, RP8, 3.5 um, 2.1×50 mm. Eluents: 5% B/A to 95% B/A in 9.0 min.(B: acetonitrile, A: 100 mM ammonia acetate buffer, pH 4.5), 0.5 mL/min.): Rt=6.273 min.

Workup

  1. customthe ice-water bath was removed
  2. additionSodium hydroxide (1.0N, 15 mL) was added
  3. customthe organic solvent was evaporated
  4. extractionThe aqueous residue was extracted with dichloromethane
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-a3ce4c7f951249a9bea2dbb0e0afddcf
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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