Tris(hydroxymethyl)aminomethane → 1-methyl-1H-imidazole-4-carboxylic acid {2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-amide

HRID 1865678Notes

Reaction equation

HRID 1865678 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7](Cl)=[O:8])[N:4]=[CH:3]1.[NH2:10][C:11]1[CH:21]=[CH:20][C:19]([C:22]2[CH:23]=[C:24]3[C:30]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[O:37][CH3:38])=[N:29][N:28]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[C:25]3=[N:26][CH:27]=2)=[CH:18][C:12]=1[C:13]([N:15]([CH3:17])[CH3:16])=[O:14].N1C=CC=CC=1.ClCCl.C(O)C(N)(CO)CO>ClCCl>[CH3:17][N:15]([CH3:16])[C:13]([C:12]1[CH:18]=[C:19]([C:22]2[CH:23]=[C:24]3[C:30]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[O:37][CH3:38])=[N:29][N:28]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:44])([CH3:46])[CH3:45])[C:25]3=[N:26][CH:27]=2)[CH:20]=[CH:21][C:11]=1[NH:10][C:7]([C:5]1[N:4]=[CH:3][N:2]([CH3:1])[CH:6]=1)=[O:8])=[O:14]

Participants

6

Reactant 4

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 21875418Pyridine methylene chlorideHCID 513419821-Methyl-1H-imidazole-4-carbonyl chlorideHCID 579757432-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanylethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide

Product 1

HCID 579758501-methyl-1H-imidazole-4-carboxylic acid {2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-amideYield 51.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Methyl-1H-imidazole-4-carbonyl chloride (0.579 mmol) was suspended in dichloromethane (4 mL) and a solution of 2-amino-5-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-N,N-dimethyl-benzamide (150 mg, 0.289 mmol) in 20% v/v pyridine/dichloromethane (1.0 mL) was added. After 16 h, PS-trisamine (Argonaut Technologies, Inc.) was added (3.0 eq. relative to acid chloride) and the suspension was filtered 3 hours later and the resin was rinsed with dichloromethane. After concentration of the filtrates in vacuo, the resulting residue was purified by silica gel chromatography to afford 1-methyl-1H-imidazole-4-carboxylic acid {2-dimethylcarbamoyl-4-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-amide (93.5 mg, 50.5%). MS: m/z 640 (M+H+).

Workup

  1. filtrationthe suspension was filtered 3 hours later
  2. washthe resin was rinsed with dichloromethane
  3. customAfter concentration of the filtrates in vacuo, the resulting residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-36c1b689bdbd42e49709e54ec5d84c9a
Source dataset
uspto-grants-2009_12
Patent number
US07626021B2

Reaction notes

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