Triethylamine → methanesulfonic acid 2-((R)-1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-oxazol-4-ylmethyl ester

HRID 245942Notes

Reaction equation

HRID 245942 reaction equation
[OH:1][CH2:2][C:3]1[N:4]=[C:5]([C@H:8]([NH:10][C:11]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([F:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[CH:14]=2)=[O:12])[CH3:9])[O:6][CH:7]=1.C(N(CC)CC)C.[CH3:48][S:49](Cl)(=[O:51])=[O:50]>ClCCl>[F:31][C:27]1[CH:26]=[C:25]2[C:30]([C:22]([C:19]3[N:20]=[C:21]4[C:13]([C:11]([NH:10][C@@H:8]([C:5]5[O:6][CH:7]=[C:3]([CH2:2][O:1][S:49]([CH3:48])(=[O:51])=[O:50])[N:4]=5)[CH3:9])=[O:12])=[CH:14][N:15]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:39])([CH3:38])[CH3:40])[C:16]4=[N:17][CH:18]=3)=[N:23][N:24]2[CH3:32])=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 712881882-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-hydroxymethyl-oxazol-2-yl)-ethyl]-amide

Product 1

HCID 86677925methanesulfonic acid 2-((R)-1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-oxazol-4-ylmethyl esterYield 114.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

In a round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-hydroxymethyl-oxazol-2-yl)-ethyl]-amide (115 mg, 0.20 mmol) was dissolved in dichloromethane (1 ml). The solution was cooled to 0° C. and triethylamine (0.04 ml, 0.29 mmol) and methanesulfonyl chloride (19 μl, 0.24 mmol) were added. The reaction mixture was stirred at 0° C. for 2 h then quenched with water and extracted with dichloromethane (2×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated to afford 147 mg of methanesulfonic acid 2-((R)-1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-oxazol-4-ylmethyl ester as a yellow foam which was used without further purification.

Workup

  1. customthen quenched with water
  2. extractionextracted with dichloromethane (2×)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ce36770dae9642d48ee4372999c03803
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

Loading…