Water → 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

HRID 246092Notes

Reaction equation

HRID 246092 reaction equation
[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7](=[O:41])[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]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[N:15](COCC[Si](C)(C)C)[CH:14]=2)=[O:12])[CH3:9])[CH2:3]1.FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7](=[O:41])[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]([Cl:31])=[CH:28][CH:29]=5)[N:24]([CH3:32])[N:23]=4)[N:20]=3)[NH:15][CH:14]=2)=[O:12])[CH3:9])[CH2:3]1

Participants

7

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 712861822-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide

Product 1

HCID 712882422-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amideYield 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(6-Chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (54 mg, 0.09 mmol) was dissolved in dichloromethane (0.9 ml) and cooled in ice bath. Trifluoroacetic acid (0.45 ml) was slowly added and the reaction was stirred at room temperature for 2.5 h. The reaction was evaporated and the residue was suspended in dichloromethane (0.9 ml). Ethylenediamine (0.36 ml, 5.4 mmol) was added and the mixture was stirred for 18 h. Water and then ethyl acetate were added to the mixture. The resulting precipitate was filtered off, rinsed with water and dried under high vacuum to give 24 mg (58%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-amide. MS: (M+H)+=470; mp=269-271° C. 1H NMR (300 MHz, DMSO-d6) δ: 9.16 (s, 1H), 8.81-8.91 (m, 1H), 8.53-8.62 (m, 1H), 8.47 (d, J=2.0 Hz, 1H), 7.97 (s, 1H), 7.25-7.33 (m, 1H), 5.27-5.52 (m, 1H), 4.95-5.11 (m, 1H), 4.18 (s, 3H), 3.96-4.12 (m, 1H), 3.73-3.92 (m, 1H), 3.61-3.72 (m, 1H), 2.08-2.35 (m, 1H), 1.38-1.48 (m, 3H).

Workup

  1. temperaturecooled in ice bath
  2. customThe reaction was evaporated
  3. stirringthe mixture was stirred for 18 h
  4. filtrationThe resulting precipitate was filtered off
  5. washrinsed with water
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-12a189439cac43c28bd780466a3ac4c2
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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