Trifluoroacetic acid → 2-(5-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)amide

HRID 246464Notes

Reaction equation

HRID 246464 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[N:12]=[C:13]3[C:19]([C:20]([NH:22][C:23]([CH3:27])([CH3:26])[CH2:24][OH:25])=[O:21])=[CH:18][N:17](COCC[Si](C)(C)C)[C:14]3=[N:15][CH:16]=1)[N:6]=[CH:5]2.FC(F)(F)C(O)=O>ClCCl>[OH:25][CH2:24][C:23]([NH:22][C:20]([C:19]1[C:13]2[C:14](=[N:15][CH:16]=[C:11]([N:7]3[C:8]4[C:4](=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=4)[CH:5]=[N:6]3)[N:12]=2)[NH:17][CH:18]=1)=[O:21])([CH3:27])[CH3:26]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 712799172-(5-Chloro-1H-indazol-1-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712884402-(5-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)amideYield 62.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(5-Chloro-1H-indazol-1-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (124 mg, 241 μmol) was dissolved in dichloromethane (3 mL) then trifluoroacetic acid (1 mL) added. After 15 h the mixture was concentrated in vacuo and Jan. 10, 1960 ammonium hydroxide/methanol/dichloromethane solution (25 mL) added. After 1 h the mixture was concentrated in vacuo and purified by chromatography (silica, 24 g Analogix column, 0-4% of methanol containing 10% ammonium hydroxide in dichloromethane) to give 2-(5-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)amide (57.7 mg, 62%) as a solid. MS (M+H)+=385; 1H NMR (DMSO-d6) δ: 9.04 (s, 1H), 8.70 (d, J=9.0 Hz, 1H), 8.53 (s, 1H), 8.43 (s, 1H), 8.07 (d, J=1.5 Hz, 1H), 7.63 (s, 1H), 7.60 (d, J=2.1 Hz, 1H), 3.59 (d, J=5.7 Hz, 2H), 1.44 (s, 6H).

Workup

  1. concentrationAfter 15 h the mixture was concentrated in vacuo and Jan
  2. addition10, 1960 ammonium hydroxide/methanol/dichloromethane solution (25 mL) added
  3. concentrationAfter 1 h the mixture was concentrated in vacuo
  4. custompurified by chromatography (silica, 24 g Analogix column, 0-4% of methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-a9c9fa047c7a42c2adb2eb011e63daa9
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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