Diisopropylethylamine → HCID 24990391, compound

HRID 600995Notes

Reaction equation

HRID 600995 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].[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH2:29][N:30]2[CH:34]=[CH:33][C:32]([NH2:35])=[N:31]2)[CH:24]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[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:35][C:32]2[CH:33]=[CH:34][N:30]([CH2:29][C:25]3[CH:24]=[N:23][CH:28]=[CH:27][CH:26]=3)[N:31]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 47002771HCID 47002771, compoundHCID 87416741HCID 87416741, compound

Product 1

HCID 24990391HCID 24990391, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 115 mg, 0.33 mmol), 1-pyridin-3-ylmethyl-1H-pyrazol-3-ylamine (72 mg, 0.41 mmol) and N,N-diisopropylethylamine (232 μL, 1.33 mmol) were combined in methylene chloride (1.7 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (139 mg, 0.37 mmol) was added and the ice bath was removed. After stirring 2 h, the reaction mixture was evaporated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate solution (1 mL) and extracted with chloroform (2×3 mL). The combined organic phases were dried over sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/chloroform to 5% methanol/chloroform) to afford (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-N-(1-pyridin-3-ylmethyl-1H-pyrazol-3-yl)-acetamide (76 mg, 46%) as a white solid after lyophilization from aqueous dioxane: LC-MS (ESI) m/e calcd for C23H24ClN5O4S [M+] 501.12, found 502 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.64 (m, 4 H, 2×CH2), 1.85 (m, 4 H, 2×CH2), 3.28 (s, 3 H, SO2CH3), 4.87 (m, 1 H, OCH), 5.26 (s, 2 H, NCH3), 6.78 (d, J=2.3 Hz, 1 H, Ar), 7.30 (dd, J=7.9, J=4.9 Hz, 1 H, Ar), 7.40 (d, J=2.3 Hz, 1 H, Ar), 7.51 (m, 1 H, Ar), 7.55 (dd, Jo=8.2, Jm=1.6 Hz, 1 H, Ar), 7.65 (d, Jm=1.6 Hz, 1 H, Ar), 8.18 (d, Jo=8.2 Hz, 1 H, Ar), 8.56 (m, 2H, Ar), 9.17 (s, 1 H, NH).

Workup

  1. temperaturecooled in an ice bath
  2. customthe ice bath was removed
  3. customthe reaction mixture was evaporated in vacuo
  4. additionThe residue was treated with saturated aqueous sodium bicarbonate solution (1 mL)
  5. extractionextracted with chloroform (2×3 mL)
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/chloroform to 5% methanol/chloroform)

Sources & evidence

ORD record
ord-f39b270dc3384feab03900c85d2daff2
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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