Trifluoroacetic acid → HCID 71288435, compound

HRID 246471Notes

Reaction equation

HRID 246471 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[C:11]2[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]=2)=[CH:4][CH:3]=1.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:8]3[C:9]4[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=4)[CH:6]=[N:7]3)[N:12]=2)[NH:17][CH:18]=1)=[O:21])([CH3:27])[CH3:26]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280554HCID 71280554, compound

Product 1

HCID 71288435HCID 71288435, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 2-(6-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 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (1 mL). After 15 h the mixture was concentrated and 25 mL of a Jan. 10, 1960 mixture of ammonium hydroxide/methanol/dichloromethane added. After 1 h the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-4% of a methanol containing 10% ammonium hydroxide solution in dichloromethane) gave 2-(6-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide (75 mg, 81%). MS (M+H)+=385; 1H NMR (DMSO-d6) δ: 8.97 (s, 1H), 8.56 (s, 2H), 8.44 (s, 1H), 7.99 (d, J=8.7 Hz, 1H), 7.64 (s, 1H), 7.36-7.48 (m, 1H), 3.62 (d, J=5.7 Hz, 2H), 1.43 (s, 6H).

Workup

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

Sources & evidence

ORD record
ord-01a50b4544824ec5b13309b1287c517c
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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