Trifluoroacetic acid → 2-(6-chloro-1-(isoxazol-3-ylmethyl)-1H-indazol-3-yl)-5-(hydroxymethyl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246452Notes

Reaction equation

HRID 246452 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]3[N:18]=[C:19]4[C:25]([C:26]([NH:28][CH:29]([CH3:31])[CH3:30])=[O:27])=[CH:24][N:23]([CH2:32][O:33]CC[Si](C)(C)C)[C:20]4=[N:21][CH:22]=3)=[N:7][N:8]2[CH2:11][C:12]2[CH:16]=[CH:15][O:14][N:13]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:17]3[N:18]=[C:19]4[C:25]([C:26]([NH:28][CH:29]([CH3:30])[CH3:31])=[O:27])=[CH:24][N:23]([CH2:32][OH:33])[C:20]4=[N:21][CH:22]=3)=[N:7][N:8]2[CH2:11][C:12]2[CH:16]=[CH:15][O:14][N:13]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280112HCID 71280112, compound

Product 1

HCID 712806192-(6-chloro-1-(isoxazol-3-ylmethyl)-1H-indazol-3-yl)-5-(hydroxymethyl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(6-Chloro-1-(isoxazol-3-ylmethyl)-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide was dissolved in dichloromethane and to this was added trifluoroacetic acid (1.79 g, 1.21 mL, 15.7 mmol). The mixture was stirred for 120 h. A precipitate had formed which was filtered off. The filtrates were concentrated in vacuo and combined with the solid to give intermediate 2-(6-chloro-1-(isoxazol-3-ylmethyl)-1H-indazol-3-yl)-5-(hydroxymethyl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (73 mg, 157 μmol). This was dissolved in 60:20:1 dichloromethane:methanol:ammonium hydroxide (10 mL), and the mixture was stirred for 2 h. The mixture was concentrated in vacuo, diluted with dichloromethane and reconcentrated to give 2-(6-chloro-1-(isoxazol-3-ylmethyl)-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (67 mg, 154 μmol, 98.1%) as a white solid. MS (M+Na)+=458; 1H NMR (CDCl3) δ: 11.97 (br. s., 1H), 9.08 (s, 1H), 8.36 (d, J=8.3 Hz, 1H), 8.29 (d, J=1.5 Hz, 1H), 8.16 (d, J=3.0 Hz, 1H), 7.98-8.07 (m, 1H), 7.46 (s, 1H), 7.12 (dd, J=8.5, 1.3 Hz, 1H), 6.21 (d, J=1.5 Hz, 1H), 5.64 (s, 2H), 4.23-4.39 (m, 1H), 1.20-1.32 (m, 6H).

Workup

  1. customA precipitate had formed which
  2. filtrationwas filtered off
  3. concentrationThe filtrates were concentrated in vacuo

Sources & evidence

ORD record
ord-ceb3c4d8339c4524aaa38c07e5ef5146
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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