Water → HCID 71285879, compound

HRID 246088Notes

Reaction equation

HRID 246088 reaction equation
[OH:1][CH2:2][C:3]([CH3:37])([CH3:36])[CH2:4][NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7].FC(F)(F)C(O)=O.C(N)CN.O>ClCCl.C(OCC)(=O)C>[OH:1][CH2:2][C:3]([CH3:37])([CH3:36])[CH2:4][NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH3:27])[N:18]=3)[N:15]=2)[NH:10][CH:9]=1)=[O:7]

Participants

7

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 6422Trifluoroacetic acidHCID 71288279HCID 71288279, compound

Product 1

HCID 71285879HCID 71285879, compoundYield 63.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(6-Fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-amide (82 mg, 0.156 mmol) was suspended in dichloromethane (1.1 ml) and cooled in ice bath. Trifluoroacetic acid (0.5 ml) was added slowly and the reaction was stirred at room temperature for 3.5 h. The reaction was evaporated and the residue was dissolved in dichloromethane (1.6 ml). Ethylenediamine (0.63 ml, 9.3 mmol) was added and the mixture was stirred at room temperature for 18 h. Water and then ethyl acetate were added to the mixture, the layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (methanol/dichloromethane) to give 39 mg (63%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-hydroxy-2,2-dimethyl-propyl)-amide as an off-white solid. (M+Na)+=419; mp=291-293° C. 1H NMR (300 MHz, DMSO-d6) δ: 9.10 (s, 1H), 8.45 (s, 1H), 8.41-8.49 (m, 1H), 8.19-8.27 (m, 1H), 7.67 (dd, J=9.8, 2.3 Hz, 1H), 7.14-7.23 (m, 1H), 4.63-4.72 (m, 1H), 4.14 (s, 3H), 3.37-3.43 (m, 2H), 3.16-3.24 (m, 2H), 0.90 (s, 6H).

Workup

  1. temperaturecooled in ice bath
  2. customThe reaction was evaporated
  3. dissolutionthe residue was dissolved in dichloromethane (1.6 ml)
  4. stirringthe mixture was stirred at room temperature for 18 h
  5. customthe layers were separated
  6. extractionthe aqueous layer was extracted twice more with ethyl acetate
  7. washThe combined organic layers were washed with sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-8d92f9e0ec534a1eafca7a792abeae17
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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