Trifluoroacetic acid → HCID 178480953, compound

HRID 432214Notes

Reaction equation

HRID 432214 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:25]3[CH2:30][CH2:29][C@@H:28]([N:31]4[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]4)[CH2:27][CH2:26]3)[N:9]=[C:10]([C:11]3[CH:12]=[C:13]([NH:17]C(=O)OC(C)(C)C)[CH:14]=[CH:15][CH:16]=3)[C:3]=12.FC(F)(F)C(O)=O>ClCCl>[NH2:17][C:13]1[CH:12]=[C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([C@H:25]3[CH2:30][CH2:29][C@@H:28]([N:31]4[CH2:32][CH2:33][N:34]([CH3:37])[CH2:35][CH2:36]4)[CH2:27][CH2:26]3)[N:9]=2)[CH:16]=[CH:15][CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178480956HCID 178480956, compound

Product 1

HCID 178480953HCID 178480953, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of cis-tert-butyl N-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)carbamate (1.7 g, 3.3 mmol, 1 equiv) and dichloromethane (40 mL) was cooled at 0° C. and then trifluoroacetic acid (10.5 mL, 137 mmol, 41 equiv) was added. The reaction mixture was allowed to warm to ambient temperature over 3 h, the solvent was removed under reduced pressure, and the residue was partitioned between CH2Cl2 (50 mL) and water (50 mL). The organic layer was separated and treated with saturated aqueous sodium bicarbonate solution (50 mL). The organic extract was dried over MgSO4, filtered, and concentrated to afford cis-3-(3-aminophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (1.34 g, 3.30 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 8.21 (1H, s), 7.17-7.21 (1H, m), 6.85 (1H, s), 6.72-6.74 (1H, m), 6.65-6.68 (1H, m), 5.36 (2H, bs), 4.75-4.80 (1H, m), 2.22-2.51 (11H, m), 2.20 (3H, s), 2.06-2.08 (2H, m), 1.58-1.68 (4H, m); RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 9.06 min. MS: MH+ 407.

Workup

  1. temperatureto warm to ambient temperature over 3 h
  2. customthe solvent was removed under reduced pressure
  3. customthe residue was partitioned between CH2Cl2 (50 mL) and water (50 mL)
  4. customThe organic layer was separated
  5. additiontreated with saturated aqueous sodium bicarbonate solution (50 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-f26a2077e8af41fca0a776cd800d0f11
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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