Maleic Acid → HCID 178488216, compound

HRID 432248

Reaction equation

HRID 432248 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]([C@H:18]3[CH2:23][CH2:22][C@H: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].[CH3:33][N:34]([CH3:44])[C:35]1[CH:43]=[CH:42][C:38]([C:39](Cl)=[O:40])=[CH:37][CH:36]=1.C(O)(=O)/C=C\C(O)=O>N1C=CC=CC=1.CCOC(C)=O>[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:39](=[O:40])[C:38]4[CH:37]=[CH:36][C:35]([N:34]([CH3:33])[CH3:44])=[CH:43][CH:42]=4)=[C:3]([O:31][CH3:32])[CH:4]=3)[C:16]=12

Participants

6

Reactant 3

HCID 444266Maleic AcidHCID 44007824-(Dimethylamino)benzoyl chlorideHCID 178488198HCID 178488198, compound

Product 1

HCID 178488216HCID 178488216, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (500 mg, 1.15 mmol) in pyridine (5 ml) was added 4-(dimethylamino)benzoylchloride (420 mg, 2.28 mol) dropwise. The solution was stirred overnight, the solvent evaporated and the residue partitioned between dichloromethane and 2N NaOH solution. The aqueous layer was extracted with dichloromethane (×3). The organics were dried, filtered and evaporated to leave a solid which was triturated with EtOAc/Et2O (1:4) to leave a solid which was dissolved in EtOAc and treated with maleic acid (3 eqs.) to give trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-4-(dimethylamino)benzamide (320 mg, 30%). 1H NMR (d6-DMSO)): δ H 9.05 (1H, s), 8.25 (1H, s), 8.18 (1H, d, J=8 Hz), 7.84 (2H, d, J=9.2 Hz), 7.29 (1H, s), 7.25 (1H, d, J=8 Hz), 6.78 (2H, d, J=8.8 Hz), 6.17 (6H, s), 4.71 (1H, m), 3.95 (3H, s), 3.01 (6H, s), 2.83-3.18 (9H, m), 2.68 (3H, s), 2.08 (6H, m), 1.56 (2H, m). HPLC (5.23 mins, 100%)

Workup

  1. customthe solvent evaporated
  2. customthe residue partitioned between dichloromethane and 2N NaOH solution
  3. extractionThe aqueous layer was extracted with dichloromethane (×3)
  4. customThe organics were dried
  5. filtrationfiltered
  6. customevaporated
  7. customto leave a solid which
  8. customwas triturated with EtOAc/Et2O (1:4)
  9. customto leave a solid which

Sources & evidence

ORD record
ord-8127a1456f174096b94187f9db63db07
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Linked notes

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