Water → N-(6-acetyl-2-chloro-3-methoxyphenyl)-4-cyclopropylthiazole-2-carboxamide

HRID 925975Notes

Reaction equation

HRID 925975 reaction equation
[CH:1]1([C:4]2[N:5]=[C:6]([C:9](Cl)=[O:10])[S:7][CH:8]=2)[CH2:3][CH2:2]1.[NH2:12][C:13]1[C:18]([Cl:19])=[C:17]([O:20][CH3:21])[CH:16]=[CH:15][C:14]=1[C:22](=[O:24])[CH3:23].O>O1CCOCC1>[C:22]([C:14]1[C:13]([NH:12][C:9]([C:6]2[S:7][CH:8]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[N:5]=2)=[O:10])=[C:18]([Cl:19])[C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 962WaterHCID 299199881-(2-Amino-3-chloro-4-methoxyphenyl)ethanoneHCID 594348264-Cyclopropyl-thiazole-2-carbonyl chloride

Product 1

HCID 59434816N-(6-acetyl-2-chloro-3-methoxyphenyl)-4-cyclopropylthiazole-2-carboxamideYield 66%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of compound 267a (3.4 g, 1.2 eq.) in dioxane (60 mL) was added 6-acetyl-2-chloro-3-methoxy aniline 201d (3.01 g, 1 eq.) in dioxane. The mixture was stirred at room temperature overnight. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate) to yield compound 268a as a brown solid in 66% yield. 1H NMR (CDCl3, 400 MHz): δ (ppm) 1-1.06 (m, 4H), 2.08-2.15 (m, 1H), 2.58 (s, 3H), 3.99 (s, 3H), 6.87 (d, J=8.78 Hz, 1H), 7.16 (s, 1H), 7.67 (d, J=8.78 Hz, 1H), 10.27 (br s, 1H); MS (ESI, EI+): m/z=351 (MH+).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-b23e6621327c41d1abe121c3c4166ec2
Source dataset
uspto-grants-2016_03
Patent number
US09284307B2

Reaction notes

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