Acetyl chloride → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-piperidin-3-ylamide

HRID 245826

Reaction equation

HRID 245826 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[C:34]5[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=5)[N:28]([CH3:36])[N:27]=4)[N:24]=3)[N:19]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:18]=2)=[O:16])[CH2:9]1)=O)(C)(C)C.C(Cl)(=O)C.C1COCC1>CO>[NH:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[C:34]5[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=5)[N:28]([CH3:36])[N:27]=4)[N:24]=3)[N:19]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[CH:18]=2)=[O:16])[CH2:9]1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8028TetrahydrofuranHCID 71280608(R)-3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 712860612-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-piperidin-3-ylamideYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
0 °C

Procedure

In a round-bottomed flask, (R)-3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (138 mg, 0.22 mmol) was suspended in methanol (2 ml). The reaction was cooled to 0° C. and acetyl chloride (0.30 ml, 4.22 mmol) was added dropwise over 10 min. The resultant bright yellow suspension was stirred at room temperature for 50 min. THF (1 ml) and methanol (1 ml) were added and stirred was continued for 1 h at room temperature then the solvent was evaporated at room temperature. The residue was suspended in dichloromethane and washed with saturated Na2CO3-solution. The aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over sodium sulfate, filtered and concentrated to afford 105 mg (90%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-piperidin-3-ylamide as a light yellow solid.

Workup

  1. stirringstirred
  2. waitwas continued for 1 h at room temperature
  3. customthe solvent was evaporated at room temperature
  4. washwashed with saturated Na2CO3-solution
  5. extractionThe aqueous layer was extracted with dichloromethane
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3771062fcaf9446cb95d350e5bc39753
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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