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

HRID 246516Notes

Reaction equation

HRID 246516 reaction equation
[OH:1][CH2:2][C:3]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]([O:27][CH3:28])=[N:19]3)[N:16]=2)[N:11](COCC[Si](C)(C)C)[CH:10]=1)=[O:8])([CH3:5])[CH3:4].FC(F)(F)C(O)=O>ClCCl>[OH:1][CH2:2][C:3]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:20]([O:27][CH3:28])=[N:19]3)[N:16]=2)[NH:11][CH:10]=1)=[O:8])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71279674N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Product 1

HCID 712839912-(3-methoxy-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)amideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-methoxy-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (101 mg, 198 mmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL). After 15 h the mixture was concentrated in vacuo then 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane solution was added. After 1 h, the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-5% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-(3-methoxy-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)amide (45 mg, 60%). MS (M+H)+=381; 1H NMR (DMSO-d6) δ: 8.94 (s, 1H), 8.62 (d, J=8.7 Hz, 1H), 8.33 (s, 1H), 7.79 (d, J=7.9 Hz, 1H), 7.61 (s, 2H), 7.28-7.38 (m, 1H), 4.19 (s, 3H), 3.62 (d, J=5.7 Hz, 2H), 1.45 (s, 6H).

Workup

  1. concentrationAfter 15 h the mixture was concentrated in vacuo
  2. addition10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane solution
  3. additionwas added
  4. concentrationthe mixture was concentrated in vacuo
  5. customPurification by chromatography (silica, 24 g Analogix column, 0-5% methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-7d1ff459924b4d53adc8dc17668ec847
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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