Potassium Carbonate → 2-(3-(2-cyclopropylethylamino)-2-oxopyrrolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

HRID 883163Notes

Reaction equation

HRID 883163 reaction equation
Br[CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[S:8][C:9]([C:13]([NH:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:14])=[C:10]([CH3:12])[N:11]=2)[C:3]1=[O:24].C(=O)([O-])[O-].[K+].[K+].[CH:31]1([CH2:34][CH2:35][NH2:36])[CH2:33][CH2:32]1>O1CCCC1.O>[CH:31]1([CH2:34][CH2:35][NH:36][CH:2]2[CH2:6][CH2:5][N:4]([C:7]3[S:8][C:9]([C:13]([NH:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=4)=[O:14])=[C:10]([CH3:12])[N:11]=3)[C:3]2=[O:24])[CH2:33][CH2:32]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 10240761CyclopropaneethanamineHCID 247992342-(3-bromo-2-oxopyrrolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide

Product 1

HCID 248016702-(3-(2-cyclopropylethylamino)-2-oxopyrrolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamideYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(3-bromo-2-oxopyrrolidin-1-yl)-N-(4-fluorobenzyl)-4-methylthiazole-5-carboxamide (0.050 g, 0.12 mmol) in a mixture of tetrahydrofuran and water (1/0.1, v/v) was added potassium carbonate (0.034 g, 0.24 mmol) and 2-cyclopropylethanamine (0.012 g, 0.15 mmol). The reaction mixture was stirred at ambient temperature for 17 hours and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexanes (3/1)) to afford the title compound as a white solid (0.030 g, 60%): mp 151-152° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 7.32-7.22 (m, 2H), 7.05-6.96 (m, 2H), 6.01 (t, J=5.6 Hz, 1H), 4.51 (d, J=5.6 Hz, 2H), 4.27-4.17 (m, 1H), 3.93-3.81 (m, 1H), 3.76-3.66 (m, 1H), 2.88-2.67 (m, 2H), 2.61 (s, 3H), 2.58-2.44 (m, 1H), 2.10-1.91 (m, 1H), 1.52-1.29 (m, 2H), 0.75-0.59 (m, 1H), 0.49-0.37 (m, 2H), 0.08-0.01 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 173.6, 162.3, 162.2, 155.2, 152.9, 133.7, 129.6, 118.6, 115.6, 59.5, 47.9, 44.9, 43.4, 35.0, 26.9, 17.3, 8.8, 4.4, 4.2; MS (ES+) m/z 417.3 (M+1).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was purified by column chromatography (ethyl acetate/hexanes (3/1))

Sources & evidence

ORD record
ord-6a334b24c5ee4254968d4f3a41e8b529
Source dataset
uspto-grants-2012_08
Patent number
US08236835B2

Reaction notes

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