Tetrahydrofuran → HCID 22346671, compound

HRID 432460Notes

Reaction equation

HRID 432460 reaction equation
[BH4-].[Na+].[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([C:26]3[CH:33]=[CH:32][C:29]([CH:30]=[O:31])=[CH:28][CH:27]=3)[N:11]=[C:12]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:15][CH:14]=3)[C:5]=12.C1COCC1>CO>[NH2:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]2[N:10]([C:26]3[CH:27]=[CH:28][C:29]([CH2:30][OH:31])=[CH:32][CH:33]=3)[N:11]=[C:12]([C:13]3[CH:14]=[CH:15][C:16]([O:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:17][CH:18]=3)[C:5]=12

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydride2×HCID 22347189HCID 22347189, compound

Product 1

HCID 22346671HCID 22346671, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium borohydride (19 mg, 0.491 mmol) was added to a solution of 4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]benzaldehyde (100 mg, 0.245 mmol) in methanol (2 mL). After 16 hours, THF (1 mL) and more sodium borohydride (19 mg, 0.491 mmol) was added. 5 hours later, the solvent was removed and water was added. The aqueous layer was extracted with dichloromathane. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using ethyl acetate/dichloromethane (80:20 to 100:0) as mobile phase to give {4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]phenyl}methanol (36 mg, 36%). 1H NMR (DMSO-d6) δ 4.56 (s, 2H), 5.27 (bs, 1H), 7.16 (m, 5H), 7.47 (m, 4H), 7.76 (d, J=8.64 Hz, 2H), 8.18 (d, J=8.52, 2H), 8.37 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+ =410.1, Rt=2.43 min.

Workup

  1. custom5 hours later, the solvent was removed
  2. additionwater was added
  3. extractionThe aqueous layer was extracted with dichloromathane
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-40d4a26d70da45d981b30cd0feca693f
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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