Dimethylformamide → 2-[[(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetyl]amino]-1,3-thiazole-5-carboxamide

HRID 600965Notes

Reaction equation

HRID 600965 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13](O)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(N(CC)C(C)C)(C)C.[NH2:33][C:34]1[S:35][C:36]([C:39]([NH2:41])=[O:40])=[CH:37][N:38]=1.CN(C)C=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]2)/[C:13]([NH:33][C:34]2[S:35][C:36]([C:39]([NH2:41])=[O:40])=[CH:37][N:38]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 162272132-Amino-1,3-thiazole-5-carboxamideHCID 87416752(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetic acid

Product 1

HCID 597451092-[[(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclohexyloxyiminoacetyl]amino]-1,3-thiazole-5-carboxamideYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclohexyloxyimino-acetic acid (prepared as in Example 9, 112 mg, 0.31 mmol), N,N-diisopropylethylamine (163 μL, 0.94 mmol) and 2-amino-thiazole-5-carboxylic acid amide (54 mg, 0.38 mmol) were combined in methylene chloride (1.5 mL) and cooled to 0° C. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 mmol) was added and the cooling bath was removed. After stirring 16 h, thin layer chromatography analysis showed no reaction. N,N-dimethylformamide (1 mL) was added and the methylene chloride was removed in vacuo. The reaction mixture was stirred 20 h more then concentrated in vacuo and purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 2% methanol/chloroform) to afford (E)-2-[2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclohexyloxyimino-acetylamino]-thiazole-5-carboxylic acid amide (33 mg, 22%) as a white solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C19H21ClN4O5S2 [M+] 484.06, found 485 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.26-1.79 (m, 8H, 4×CH2), 2.00 (m, 2H, 2×CH of CH2), 3.32 (s, 3 H, SO2CH3), 4.40 (m, 1 H, OCH), 5.82 (brs, 2 H, NH2), 7.64 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.74 (d, Jm=1.5 Hz, 1 H, Ar), 7.96 (s, 1H, Ar), 8.23 (d, Jo=8.2 Hz, 1 H, Ar), 10.23 (s, 1 H, NH).

Workup

  1. customthe cooling bath was removed
  2. customno reaction
  3. customthe methylene chloride was removed in vacuo
  4. stirringThe reaction mixture was stirred 20 h more
  5. concentrationconcentrated in vacuo
  6. custompurified by flash column chromatography (Merck silica gel 60, 40-63 μm; 2% methanol/chloroform)

Sources & evidence

ORD record
ord-9967d6aaddcf4849a572d2e0d43e3221
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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