Sodium hydride → HCID 11634686, compound

HRID 408526Notes

Reaction equation

HRID 408526 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][C:5]1[S:9][C:8]([NH:10][C:11]([C:13]2([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[CH2:15][CH2:14]2)=[O:12])=[N:7][CH:6]=1.Br.Br[CH2:30][CH2:31][N:32]([CH2:35][CH3:36])[CH2:33][CH3:34].[H-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:27]=[CH:26][CH:25]=[CH:24][C:3]=1[CH2:4][C:5]1[S:9][C:8](=[N:10][C:11]([C:13]2([C:16]3[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=3)[CH2:15][CH2:14]2)=[O:12])[N:7]([CH2:30][CH2:31][N:32]([CH2:35][CH3:36])[CH2:33][CH3:34])[CH:6]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 706072-Bromoethyldiethylammonium bromideHCID 11538561HCID 11538561, compound

Product 1

HCID 11634686HCID 11634686, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(4-Methoxy-phenyl)-cyclopropanecarboxylic acid [5-(2-chloro-benzyl)-thiazol-2-yl]-amide (39.9 mg, 0.100 mmol) and (2-bromo-ethyl)-diethyl-amine hydrobromide (26.1 mg, 0.100 mmol) were dissolved in 1 mL of tetrahydrofuran. Sodium hydride (60% dispersion in oil, 8.8 mg, 0.22 mmol) was added and the reaction was subjected to microwave irradiation for 10 minutes at 100° C. The solvent was evaporated to dryness and the crude mixture was purified by reverse-phase preparative liquid chromatography to yield 1-(4-methoxy-phenyl)-cyclopropanecarboxylic acid [5-(2-chloro-benzyl)-3-(2-diethylamino-ethyl)-3H-thiazol-2-ylidene]-amide (10 mg, 0.020 mmol, 20%) ESI-MS m/z calc. 497.2. found 498.3 (M+1)+. Retention time of 2.64 minutes. 1H NMR (400 MHz, CD3CN) δ 1.07-1.17 (m, 8H), 1.54-1.59 (m, 2H), 2.88-2.94 (m, 4H), 3.19-3.24 (m, 2H), 3.80 (s, 3H), 4.07 (s, 2H), 4.24 (t, J=6.4 Hz, 2H), 6.86-6.91 (m, 2H), 6.97 (s, 1H), 7.26-7.47 (m, 6H) and 1-(4-methoxy-phenyl)-cyclopropanecarboxylic acid [5-(2-chloro-benzyl)-thiazol-2-yl]-(2-diethylamino-ethyl)-amide (14 mg, 0.028 mmol, 28%) ESI-MS m/z calc. 497.2. found 498.3 (M+1)+. Retention time of 2.65 minutes. 1H NMR (400 MHz, CD3CN) δ 1.08-1.17 (m, 6H), 1.30-1.37 (m, 2H), 1.51-1.57 (m, 2H), 2.55-2.59 (m, 2H), 3.00-3.05 (m, 4H), 3.79 (s, 3H), 4.26 (s, 2H), 4.42 (t, J=3.0 Hz, 2H), 6.90-6.95 (m, 2H), 7.16-7.23 (m, 2H), 7.27-7.50 (m, 5H).

Workup

  1. customirradiation for 10 minutes at 100° C
  2. customThe solvent was evaporated to dryness
  3. customthe crude mixture was purified by reverse-phase preparative liquid chromatography

Sources & evidence

ORD record
ord-43c6ecbdd85f4bcbbbad34efb4d853b0
Source dataset
uspto-grants-2014_06
Patent number
US08759335B2

Reaction notes

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