Aniline → HCID 178488231, compound

HRID 432352Notes

Reaction equation

HRID 432352 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]3[CH2:23][CH2:22][CH:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:40][C:41](Cl)=[O:42].[NH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>CN(C=O)C>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:41](=[O:42])[CH2:40][NH:44][C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

Participants

6

Reactant 4

HCID 6115AnilineHCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 208170343-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)-cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 1

HCID 178488231HCID 178488231, compoundYield 4.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.151 g, 0.356 mmol, 1 equiv), potassium carbonate (0.098 g, 0.711 mmol, 2 equiv), and chloroacetylchloride (0.04 mL, 0.5 mmol, 1.5 equiv) in DMF (1.5 mL) was stirred at ambient temperature for 20 minutes and then aniline (0.32 mL, 3.5 mmol, 10 equiv) was added. The reaction mixture was stirred at ambient temperature for 72 h. The solvent was removed under reduced pressure and the residue was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was washed with saturated aqueous sodium bicarbonate (10 mL) and then extracted with CH2Cl2 (25 mL). The organic extract was dried over MgSO4, filtered, and concentrated to give cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2-anilinoacetamide as a yellow solid (0.010 g, 0.017 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 9.30 (1H, s), 8.35-8.38 (1H, m), 8.21 (1H, s), 7.21-7.23 (2H, m), 7.12-7.16 (2H, m), 6.64-6.66 (3H, m), 6.31-6.34 (1H, m), 4.77-4.81 (1H, m), 3.90 (2H, d, J=6.0 Hz), 3.82 (3H, s), 2.21-2.51 (11H, m), 2.16 (3H, s), 2.06-2.08 (2H, m), 1.55-1.70 (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 12.37 min. MS: MH+ 570.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 72 h
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min)
  4. customThe acetonitrile was removed in vacuo
  5. washthe aqueous mixture was washed with saturated aqueous sodium bicarbonate (10 mL)
  6. extractionextracted with CH2Cl2 (25 mL)
  7. extractionThe organic extract
  8. dry with materialwas dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-604bd3bbbb40483b9b7620bc54c44d8e
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

Loading…