Diisopropylethylamine → HCID 24990390, compound

HRID 600992Notes

Reaction equation

HRID 600992 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].[NH2:23][C:24]1[CH:28]=[CH:27][N:26]([CH2:29][C:30]2[CH:31]=[C:32]([NH:36][C:37](=[O:39])[CH3:38])[CH:33]=[CH:34][CH:35]=2)[N:25]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:37]([NH:36][C:32]1[CH:31]=[C:30]([CH:35]=[CH:34][CH:33]=1)[CH2:29][N:26]1[CH:27]=[CH:28][C:24]([NH:23][C:13](=[O:15])/[C:12](/[C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)=[N:16]/[O:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:25]1)(=[O:39])[CH3:38]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 67482459HCID 67482459, compoundHCID 87416741HCID 87416741, compound

Product 1

HCID 24990390HCID 24990390, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(E)-(3-Chloro-4-methanesulfonyl-phenyl)-cyclopentyloxyimino-acetic acid (prepared as in Example 1, 100 mg, 0.29 mmol), N-[3-(3-amino-pyrazol-1-ylmethyl)-phenyl]-acetamide (67 mg, 0.29 mmol) and N,N-diisopropylethylamine (151 μL, 0.87 mmol) were combined in methylene chloride (1.5 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (110 mg, 0.29 mmol) was added and the ice bath was removed. 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 80% ethyl acetate/hexanes) to afford (E)-N-[1-(3-acetylamino-benzyl)-1H-pyrazol-3-yl]-2-(3-chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetamide (67 mg, 42%) as a white solid after lyophilization from aqueous acetonitrile: LC-MS (ESI) m/e calcd for C26H28ClN5O5S [M+] 557.15, found 558 [M+H+]; H1-NMR (400 MHz, CDCl3) δ ppm 1.63 (m, 4 H, 2×CH2), 1.84 (m, 4 H, 2×CH2), 2.16 (s, 3 H, CO2CH3), 3.29 (s, 3 H, SO2CH3), 4.86 (m, 1 H, OCH), 5.20 (s, 2H, NCH2), 6.75 (d, J=2.3 Hz, 1 H, Ar), 6.92 (brd, J=7.7 Hz, 1 H, Ar), 7.29 (brt, J=8.0 Hz, 1 H, Ar), 7.37 (m, 3 H, 2 Ar and NH), 7.43 (brd, J=7.9 Hz, 1 H, Ar), 7.54 (dd, Jo=8.2, Jm=1.5 Hz, 1 H, Ar), 7.64 (d, Jm=1.5 Hz, 1 H, Ar), 8.17 (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. additionThe residue was treated with saturated aqueous sodium bicarbonate solution (1 mL)
  4. extractionextracted with chloroform (2×3 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 50% ethyl acetate/chloroform to 80% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9823288e05384703b27ed06cd6ffe6a5
Source dataset
uspto-grants-2011_03
Patent number
US07902248B2

Reaction notes

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