Diisopropylethylamine → HCID 24990020, compound

HRID 600969Notes

Reaction equation

HRID 600969 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(N(CC)C(C)C)(C)C.[NH2:32][C:33]1[S:34][C:35]([C:38]([NH2:40])=[O:39])=[CH:36][N:37]=1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)/[C:13]([NH:32][C:33]2[S:34][C:35]([C:38]([NH2:40])=[O:39])=[CH:36][N:37]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 162272132-Amino-1,3-thiazole-5-carboxamideHCID 87416741HCID 87416741, compound

Product 1

HCID 24990020HCID 24990020, compoundYield 12.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 96 mg, 0.28 mmol), N,N-diisopropylethylamine (145 μL, 0.83 mmol) and 2-amino-thiazole-5-carboxylic acid amide (prepared as in Example 12, 48 mg, 0.34 mmol) were combined in acetonitrile (1.4 mL) and cooled to 0° C. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (106 mg, 0.28 mmol) was added and the cooling bath was removed. After stirring 16 h, the reaction mixture was treated with saturated aqueous sodium bicarbonate solution (30 mL) and extracted with 10% methanol/chloroform (3×35 mL). The combined organic phases were dried over magnesium sulfate and evaporated in vacuo. The residue was 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-cyclopentyloxyimino-acetylamino]-thiazole-5-carboxylic acid amide (16 mg, 12%) as a white solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C18H19ClN4O5S2 [M+] 470.05, found 471 [M+H+]: H1-NMR (400 MHz, CD3OD) δ ppm 1.66 (m, 4 H, 2×CH2), 1.92 (m, 4 H, 2×CH2), 3.34 (s, 3 H, SO2CH3), 5.04 (m, 1 H, OCH), 7.66 (dd, Jo=8.2, Jm=1.6 Hz, 1 H, Ar), 7.78 (d, Jm=1.6 Hz, 1 H, Ar), 8.05 (s, 1H, Ar), 8.17 (d, Jo=8.2 Hz, 1 H, Ar).

Workup

  1. customthe cooling bath was removed
  2. additionthe reaction mixture was treated with saturated aqueous sodium bicarbonate solution (30 mL)
  3. extractionextracted with 10% methanol/chloroform (3×35 mL)
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 2% methanol/chloroform)

Sources & evidence

ORD record
ord-fdc30729bd4f428abee138b6199de3ca
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

Loading…