Trifluoroacetic acid → HCID 71288434, compound

HRID 246524Notes

Reaction equation

HRID 246524 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]([CH:27]4[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]4)=[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]([CH:27]4[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]4)=[N:19]3)[N:16]=2)[NH:11][CH:10]=1)=[O:8])([CH3:5])[CH3:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71280223HCID 71280223, compound

Product 1

HCID 71288434HCID 71288434, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-(1-hydroxy-2-methylpropan-2-yl)-2-(3-(1-methylpiperidin-4-yl)-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (57 m g, 98.7 μmol) 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 added. After 1 h the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-6% methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-[3-(1-methyl-piperidin-4-yl)indazol-1-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (2-hydroxy-1,1-dimethyl-ethyl)amide (10 mg, 23%). MS (M+H)+=447; 1H NMR (DMSO-d6) δ: 9.00 (s, 1H), 8.64 (d, J=8.5 Hz, 1H), 8.37 (s, 1H), 7.99 (d, J=7.9 Hz, 1H), 7.65 (s, 1H), 7.57 (t, J=7.3 Hz, 1H), 7.35 (t, J=7.5 Hz, 1H), 5.06 (t, J=5.7 Hz, 2H), 3.62 (d, J=5.7 Hz, 2H), 2.98 (d, J=11.5 Hz, 2H), 2.30 (s, 3H), 1.94-2.24 (m, 5H), 1.44 (s, 6H)

Workup

  1. concentrationAfter 15 h the mixture was concentrated in vacuo
  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, 0-6% methanol containing 10% ammonium hydroxide in dichloromethane)

Sources & evidence

ORD record
ord-4fd9000ea18c469f93bf5bef35fbd75c
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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