1,2-Dichloroethane → 2-{[2-(4-Isopropyl-phenoxy)-acetylamino]-methyl}-thiazole-4-carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide

HRID 1009204Notes

Reaction equation

HRID 1009204 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][NH:10][C:11]([C:13]2[N:14]=[C:15]([CH2:18][NH2:19])[S:16][CH:17]=2)=[O:12])[CH:5]=[CH:6][CH:7]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH:34]([C:37]1[CH:47]=[CH:46][C:40]([O:41][CH2:42][C:43](O)=[O:44])=[CH:39][CH:38]=1)([CH3:36])[CH3:35]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][NH:10][C:11]([C:13]2[N:14]=[C:15]([CH2:18][NH:19][C:43](=[O:44])[CH2:42][O:41][C:40]3[CH:46]=[CH:47][C:37]([CH:34]([CH3:35])[CH3:36])=[CH:38][CH:39]=3)[S:16][CH:17]=2)=[O:12])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 1371314-Isopropylphenoxyacetic acidHCID 577870612-Aminomethyl-thiazole-4-carboxylic acid [2-(3-chlorophenyl)ethyl]amide

Product 1

HCID 577870152-{[2-(4-Isopropyl-phenoxy)-acetylamino]-methyl}-thiazole-4-carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amideYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-Aminomethyl-thiazole-4-carboxylic acid [2-(3-chloro-phenyl)-ethyl]-amide (50 mg, 0.17 mmol) was dissolved in DMF (1 mL). EDC (38 mg, 0.2 mmol) and HOBt (27 mg, 0.2 mmol) where added and the mixture was stirred at ambient temperature for 10 minutes. (4-Isopropyl-phenoxy)-acetic acid (33 mg, 0.17 mmol) was added. The reaction mixture was stirred at ambient temperature for 18 hours. DI water was added and the mixture was extracted with ethyl acetate ×3. The combined organic layers were washed with 1 N hydrochloric acid ×2, 2 N sodium hydroxide ×2, 1 N sodium bicarbonate ×2, DI water ×2 and brine ×1, dried over sodium sulfate, filtered and concentrated in vacuo to give a yellow oil. The oil was purified by column chromatography using silica (1:1 Ethyl acetate:Hexanes) to give the title compound as a semi-solid (16.8 mg, 21%). 1H NMR (400 MHz, d6-DMSO): 9.02 (t, 1H), 8.41 (t, 1H), 8.11 (s, 1H), 7.27 (m, 3H), 7.16 (m, 3H), 6.88 (d, 2H), 4.61 (d, 2H), 4.56 (s, 2H), 3.48 (q, 2H), 2.83 (m, 3H), 1.17 (d, 6H); MS (ESI-LCMS) for C24H27ClN3O3S: 472 (MH+).

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature for 18 hours
  2. extractionthe mixture was extracted with ethyl acetate ×3
  3. washThe combined organic layers were washed with 1 N hydrochloric acid ×2, 2 N sodium hydroxide ×2, 1 N sodium bicarbonate ×2, DI water ×2 and brine ×1
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a yellow oil
  8. customThe oil was purified by column chromatography

Sources & evidence

ORD record
ord-26973750ab7541f8a09af6dd5a99d28f
Source dataset
uspto-grants-2011_07
Patent number
US07973061B2

Reaction notes

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