Iodoethane → (S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-ethyl-1H-imidazole-4-carboxamide

HRID 872803Notes

Reaction equation

HRID 872803 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[CH:23][NH:24][CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[H-].[Na+].I[CH2:29][CH3:30]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:14]=[CH:13][N:12]([CH2:15][C@@H:16]([NH:18][C:19]([C:21]3[N:22]=[CH:23][N:24]([CH2:29][CH3:30])[CH:25]=3)=[O:20])[CH3:17])[N:11]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 178461751(S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide

Product 1

HCID 70656247(S)-N-{1-[3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1-ethyl-1H-imidazole-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(S)—N-{1-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]propan-2-yl}-1H-imidazole-4-carboxamide (250 mg, 0.705 mmol) in dry DMF (3 ml) was added slowly to the mixture of dry DMF (1 ml) and 55% NaH (61.4 mg, 1.41 mmol) at 0° C. under an nitrogen atmosphere. Thereafter the reaction mixture was stirred at RT for 30 min. The reaction mixture was recooled to 0° C. Iodoethane (0.057 ml, 0.712 mmol) was slowly added at 0° C. and then the reaction mixture was stirred at RT overnight. The reaction mixture was quenched with brine (20 ml), pH was adjusted over 9 with NaOH and the product was extracted into ethyl acetate (3×30 ml). The combined organic layers were washed with water, dried and concentrated. Flash chromatography on silica gel by using CH2Cl2-MeOH as a gradient eluent (100:0-99:1) afforded the title product. 1H NMR (400 MHz, DMSO-d6): 1.07 (3H, d), 1.34 (3H, t), 4.02 (2H, q), 4.20 (1H, distorted dd), 4.34 (2H, m), 6.95 (1H, d), 7.67 (1H, d), 7.76 (1H, d), 7.84 (1H, d), 8.00 (2H, m), 8.20 (1H, d), 8.27 (1H, d).

Workup

  1. customwas recooled to 0° C
  2. stirringthe reaction mixture was stirred at RT overnight
  3. customThe reaction mixture was quenched with brine (20 ml)
  4. extractionthe product was extracted into ethyl acetate (3×30 ml)
  5. washThe combined organic layers were washed with water
  6. customdried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-dc5e90dfd0be436f86c536e47cb3d4ef
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

Loading…