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

HRID 245827Notes

Reaction equation

HRID 245827 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[N:12]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:11]=2)=[O:9])[CH2:2]1.C(N(CC)CC)C.[CH3:45][S:46](Cl)(=[O:48])=[O:47]>ClCCl>[CH3:45][S:46]([N:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([C:19]4[C:27]5[C:22](=[CH:23][C:24]([Cl:28])=[CH:25][CH:26]=5)[N:21]([CH3:29])[N:20]=4)[N:17]=3)[N:12]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[CH:11]=2)=[O:9])[CH2:2]1)(=[O:48])=[O:47]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 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-ylamide

Product 1

HCID 712881522-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methanesulfonyl-piperidin-3-yl)-amideYield 90.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (R)-piperidin-3-ylamide (104 mg, 0.19 mmol) in dichloromethane (1.5 ml) at 0° C. was added triethylamine (0.04 ml, 0.29 mmol) followed by methanesulfonyl chloride (0.02 ml, 0.26 mmol). The reaction mixture was stirred at room temperature overnight then quenched with water and extracted with dichloromethane (2×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-4% MeOH) then triturated with ethyl acetate to afford 106 mg (89%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methanesulfonyl-piperidin-3-yl)-amide as a light yellow solid.

Workup

  1. customthen quenched with water
  2. extractionextracted with dichloromethane (2×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-4% MeOH)
  7. customthen triturated with ethyl acetate

Sources & evidence

ORD record
ord-40bd011298f0453aa3992e3791660c24
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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