2-Phenylisobutyric acid → HCID 178476565, compound

HRID 897629Notes

Reaction equation

HRID 897629 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][CH:3]=1.[CH3:31][C:32]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([CH3:36])[C:33]([OH:35])=[O:34].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:33]([OH:35])(=[O:34])[CH3:32].[C:33]([OH:35])(=[O:34])[CH3:32].[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:4]=[CH:3][C:2]([NH:1][C:33](=[O:34])[C:32]([CH3:31])([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[CH3:36])=[CH:7][CH:6]=3)[C:16]=12

Participants

7

Reactant 5

HCID 132222-Phenylisobutyric acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178480983HCID 178480983, compound

Product 1

HCID 178476565HCID 178476565, compoundYield 23.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution containing cis-3-(4-aminophenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.1 g, 0.000246 mol), α,α-dimethylphenylacetic acid (0.045 g, 0.000271 mol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.071 g, 0.000369 mol) and 1-hydroxy-7-azabenzotriazole (0.0037 g, 0.000271 mol) in anhydrous N,N-Dimethylformamide (5 mL) was stirred for 5 min., N,N-diisopropylethylamine (0.098 g, 0.00076 mol) was added dropwise and stirring under an atmosphere of nitrogen was continued for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1M ammonium acetate over 25 min, 21 mL/min) to yield cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-2-methyl-2-phenylpropanamide diacetate (0.014 g, 0.000021 mol) as a white solid.

Workup

  1. stirringstirring under an atmosphere of nitrogen
  2. waitwas continued for 16 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue was purified by preparative HPLC (Hypersil C18, 8 μm, 25 cm; 10-60% acetonitrile-0.1M ammonium acetate over 25 min, 21 mL/min)

Sources & evidence

ORD record
ord-7213a072f743460a9acad0dfb6d0fc3d
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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