Water → HCID 118284057, compound

HRID 526017Notes

Reaction equation

HRID 526017 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]2[NH:8][C:9]([C:11](=[O:28])[NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:14]([F:17])([F:16])[F:15])=[CH:10][C:5]2=[CH:4][C:3]=1[CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34].[H-].[Na+].I[CH2:41][CH3:42].O>CN(C)C=O.C(OCC)(=O)C>[CH2:41]([N:8]1[C:6]2=[N:7][C:2]([CH3:1])=[C:3]([CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:36])[CH3:35])[CH:4]=[C:5]2[CH:10]=[C:9]1[C:11](=[O:28])[NH:12][CH:13]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:26])[F:27])[CH:19]=1)[C:14]([F:15])([F:16])[F:17])[CH3:42]

Participants

7

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 131735593HCID 131735593, compound

Product 1

HCID 118284057HCID 118284057, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl {[6-methyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}carbamate (410 g, 0.77 mmol) was dissolved under argon at 0° C. in N,N-dimethylformamide (7.9 ml). Sodium hydride (60%; 37 mg, 0.92 mmol) was added and the mixture was stirred with ice cooling for 2 h. Iodoethane (145 g, 0.92 mmol) was added and the reaction mixture was thawed with stirring over 18 h. Water and ethyl acetate were added and the phases were separated. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (3/1) and gave 300 g (68% of theory) of tert-butyl a {[1-ethyl-6-methyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]methyl}carbamate. HPLC-MS: log P=4.67; mass (m/z): 559.2 (M+H)+; 1HNMR (D6-DMSO): δ 1.21 (t, 2H), 1.40 (s, 9H), 3.32 (s, 3H), 4.21 (m, 2H), 4.57 (q, 2H), 6.28-6.32 (m, 1H), 7.29 (s, 1H), 7.37 (m, 1H), 7.70-7.87 (m, 2H), 8.06 (d, 1H), 8.20 (s, 1H), 9.67 (m, 1H).

Workup

  1. stirringwith stirring over 18 h
  2. customthe phases were separated
  3. washThe organic phase was washed with saturated sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was chromatographed with cyclohexane/ethyl acetate (3/1)

Sources & evidence

ORD record
ord-bb4dd35e728741ab9ac30db2b5cec39b
Source dataset
uspto-grants-2016_05
Patent number
US09345247B2

Reaction notes

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