Pyridine → 2-{[2-(4-Trifluoromethoxyphenoxy)-acetylamino]-methyl}thiazole-4-carboxylic acid [2-(3-chlorophenyl)-ethyl]amide

HRID 1009196Notes

Reaction equation

HRID 1009196 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.[F:20][C:21]([F:35])([F:34])[O:22][C:23]1[CH:33]=[CH:32][C:26]([O:27][CH2:28][C:29](Cl)=[O:30])=[CH:25][CH:24]=1.N1C=CC=CC=1.[NH4+].[Cl-]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[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:29](=[O:30])[CH2:28][O:27][C:26]3[CH:32]=[CH:33][C:23]([O:22][C:21]([F:34])([F:20])[F:35])=[CH:24][CH:25]=3)[S:16][CH:17]=2)=[O:12])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 25517Ammonium ChlorideHCID 27773084-(Trifluoromethoxy)phenoxyacetyl chlorideHCID 577870612-Aminomethyl-thiazole-4-carboxylic acid [2-(3-chlorophenyl)ethyl]amide

Product 1

HCID 116492242-{[2-(4-Trifluoromethoxyphenoxy)-acetylamino]-methyl}thiazole-4-carboxylic acid [2-(3-chlorophenyl)-ethyl]amide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

2-Aminomethyl-thiazole-4-carboxylic acid [2-(3-chlorophenyl)ethyl]amide (0.54 g, 1.8 mmol) was dissolved in methylene chloride (15 mL). (4-Trifluoromethoxyphenoxy)-acetyl chloride (0.47 g, 1.8 mmol) was added followed by pyridine (0.3 mL, 4 mmol) and DMAP (0.02 g, 0.1 mmol). The mixture was stirred for 12 hours. Saturated, aqueous NH4Cl was added and the mixture was extracted with methylene chloride ×3. The combined organic extracts were washed with 1N HCl, saturated, aqueous NaHCO3, brine, dried over sodium sulfate, filtered and concentrated in vacuo. The material was purified by recrystallization from ethanol/diethyl ether to afford the title compound (0.65 g, 68% from the Boc protected amine): 1H NMR (400 MHz, d6-DMSO): 9.08 (t, 1H), 8.40 (t, 1H), 8.10 (s, 1H), 7.27 (m, 5H), 7.17 (d, 1H), 7.06 (d, 2H), 4.65 (s, 2H), 4.62 (d, 2H), 3.48 (m, 2H), 2.84 (t, 2H); MS (ESI-LCMS) for C22H20ClF3N3O4S: 514 (MH+).

Workup

  1. extractionthe mixture was extracted with methylene chloride ×3
  2. washThe combined organic extracts were washed with 1N HCl
  3. dry with materialsaturated, aqueous NaHCO3, brine, dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe material was purified by recrystallization from ethanol/diethyl ether

Sources & evidence

ORD record
ord-11890b3697214923a219aecc93b4e47c
Source dataset
uspto-grants-2011_07
Patent number
US07973061B2

Reaction notes

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