Acetic Acid → HCID 22347037, compound

HRID 432488Notes

Reaction equation

HRID 432488 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH2:15][C:16]1[N:21]=[CH:20][N:19]=[C:18]2[N:22]([C:38]3[CH:45]=[CH:44][C:41]([CH:42]=O)=[CH:40][CH:39]=3)[N:23]=[C:24]([C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:27][CH:26]=3)[C:17]=12.[CH3:46][N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1.C(O)(=O)C.C(=O)(O)[O-].[Na+]>ClC(Cl)C.O>[CH3:46][N:47]1[CH2:52][CH2:51][N:50]([CH2:42][C:41]2[CH:44]=[CH:45][C:38]([N:22]3[C:18]4=[N:19][CH:20]=[N:21][C:16]([NH2:15])=[C:17]4[C:24]([C:25]4[CH:30]=[CH:29][C:28]([O:31][C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)=[CH:27][CH:26]=4)=[N:23]3)=[CH:39][CH:40]=2)[CH2:49][CH2:48]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 22347189HCID 22347189, compound

Product 1

HCID 22347037HCID 22347037, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

Sodium triacetoxyborohydride (67 mg, 0.319 mmol) was added to a mixture of 4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]benzaldehyde (100 mg, 0.245 mmol), 4-methylpiperazine (37 mg, 0.369 mmol), glacial acetic acid (35 mg, 0.589 mmol) in dichloroethane (4 mL). After stirring at room temperature over night, more sodium triacetoxyborohydride (67 mg, 0.319 mmol) was added and the reaction mixture was stirred over night. Water (2 mL) was added and followed by sodium bicarbonate (250 mg). After stirring vigorously for 1 hour, the layers were separated and the aqueous layer 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 (97:3 to 80:20) as mobile phase to give 1-{4-[(4-methylpiperazino)methyl]phenyl}-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (25 mg, 21%). 1H NMR (DMSO-d6) δ 2.30 (s, 3H), 2.48 (bm, 8H), 3.56 (s, 3H), 5.75 (bs, 2H), 7.11 (d, J=8.50, 2H), 7.18 (m, 3H), 7.40 (m, 2H), 7.48 (d, J=8.50 Hz, 2H), 7.29 (d, J=8.63 Hz, 2H), 8.12 (d, J=8.50 Hz, 2H), 8.47 (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+=492.2, Rt=2.97 min.

Workup

  1. stirringthe reaction mixture was stirred over night
  2. stirringAfter stirring vigorously for 1 hour
  3. customthe layers were separated
  4. extractionthe aqueous layer 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-190074bc7e884479a59633a4a08d58fe
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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