Diisopropylethylamine → methyl 4-[[3-[[(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyiminoacetyl]amino]pyrazol-1-yl]methyl]benzoate

HRID 600968Notes

Reaction equation

HRID 600968 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].[CH3:23][O:24][C:25](=[O:39])[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][N:33]2[CH:37]=[CH:36][C:35]([NH2:38])=[N:34]2)=[CH:28][CH:27]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:23][O:24][C:25](=[O:39])[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][N:33]2[CH:37]=[CH:36][C:35]([NH:38][C:13](=[O:15])/[C:12](/[C:4]3[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=3)=[N:16]/[O:17][CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[N:34]2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 54920827Methyl 4-[(3-amino-1H-pyrazol-1-yl)methyl]benzoateHCID 87416741HCID 87416741, compound

Product 1

HCID 24990019methyl 4-[[3-[[(2E)-2-(3-chloro-4-methylsulfonylphenyl)-2-cyclopentyloxyiminoacetyl]amino]pyrazol-1-yl]methyl]benzoateYield 74.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-(3-chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 157 mg, 0.45 mmol), 4-(3-amino-pyrazol-1-ylmethyl)-benzoic acid methyl ester (117 mg, 0.50 mmol) and N,N-diisopropylethylamine (237 μL, 1.36 mmol) were combined in methylene chloride (20 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (173 mg, 0.45 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/hexanes) to afford (E)-4-{3-[2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester (188 mg, 74%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C26H27ClN4O6S [M+] 558.13, found 559 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.63 (m, 4 H, 2×CH2), 1.85 (m, 4 H, 2×CH2), 3.29 (s, 3 H, SO2CH3), 3.92 (s, 3 H, CO2CH3), 4.86 (m, 1 H, OCH), 5.29 (s, 2H, NCH2), 6.79 (d, J=2.3 Hz, 1 H, Ar), 7.23 (d, J=8.3 Hz, 2 H, Ar), 7.40 (d, J=2.3 Hz, 1 H, Ar), 7.55 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.65 (d, Jm=1.5 Hz, 1 H, Ar), 8.02 (d, J=8.3 Hz, 2 H, Ar), 8.18 (d, Jo=8.2 Hz, 1 H, Ar), 9.20 (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/hexanes)

Sources & evidence

ORD record
ord-f2dd779257794321ae0747b22f1233e5
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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