Acetyl chloride → 2-(5-difluoromethoxy-1-piperidin-4-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide hydrochloride

HRID 246303

Reaction equation

HRID 246303 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:22]3[C:17](=[CH:18][C:19]([O:23][CH:24]([F:26])[F:25])=[CH:20][CH:21]=3)[C:16]([C:27]3[N:28]=[C:29]4[C:35]([C:36](=[O:42])[NH:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][N:33]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[C:30]4=[N:31][CH:32]=3)=[N:15]2)[CH2:10][CH2:9]1)=O)(C)(C)C.C([Cl:54])(=O)C>CO>[ClH:54].[C:38]([NH:37][C:36]([C:35]1[C:29]2[C:30](=[N:31][CH:32]=[C:27]([C:16]3[C:17]4[C:22](=[CH:21][CH:20]=[C:19]([O:23][CH:24]([F:25])[F:26])[CH:18]=4)[N:14]([CH:11]4[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[N:15]=3)[N:28]=2)[N:33]([CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[CH:34]=1)=[O:42])([CH3:41])([CH3:40])[CH3:39]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 712798134-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 712798372-(5-difluoromethoxy-1-piperidin-4-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide hydrochlorideYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

In a round-bottomed flask, 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (102 mg, 0.143 mmol) was suspended in methanol (1.4 ml). The suspension was cooled to 0° C. and acetyl chloride (0.20 ml, 2.81 mmol) was added dropwise. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 h. The solvent was evaporated at room temperature and the residue dried under high vacuum to afford 92 mg (99%) of 2-(5-difluoromethoxy-1-piperidin-4-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide hydrochloride as a yellow solid which was used without further purification.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. customThe solvent was evaporated at room temperature
  4. customthe residue dried under high vacuum

Sources & evidence

ORD record
ord-905ee059d92143cd86287d0a174cae03
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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