Triethylamine → N-cyclobutyl-N'-[1-(3-{1-ethyl-3-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-5-yl}phenyl)-1-methylethyl]sulfamide

HRID 540752Notes

Reaction equation

HRID 540752 reaction equation
[CH:1]1([NH:5][S:6](Cl)(=[O:8])=[O:7])[CH2:4][CH2:3][CH2:2]1.[CH2:10]([N:12]1[C:16]([C:17]2[CH:18]=[C:19]([C:23]([NH2:26])([CH3:25])[CH3:24])[CH:20]=[CH:21][CH:22]=2)=[CH:15][C:14]([O:27][C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[N:13]1)[CH3:11].C(N(CC)CC)C>ClCCl>[CH:1]1([NH:5][S:6]([NH:26][C:23]([C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([C:16]3[N:12]([CH2:10][CH3:11])[N:13]=[C:14]([O:27][C:28]4[CH:29]=[CH:30][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:32][CH:33]=4)[CH:15]=3)[CH:18]=2)([CH3:25])[CH3:24])(=[O:8])=[O:7])[CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22326606N-cyclobutylsulfamoyl chlorideHCID 671115902-(3-{1-ethyl-3-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-5-yl}phenyl)propan-2-amine

Product 1

HCID 67111133N-cyclobutyl-N'-[1-(3-{1-ethyl-3-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-5-yl}phenyl)-1-methylethyl]sulfamideYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of cyclobutylsulfamoyl chloride (0.65 M in CH2Cl2, 3.0 mL, 1.9 mmol, 1.5 equiv) was added to a solution of 2-(3-{1-ethyl-3-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-5-yl}phenyl)propan-2-amine (0.50 g, 1.3 mmol, 1 equiv) and triethylamine (1.1 mL, 7.7 mmol, 6.0 equiv) in dichloromethane at −78° C. The reaction mixture was stirred for 10 minutes at −78° C., then cooling bath was removed. Stirred an additional 20 minutes, then partitioned between dichloromethane and aqueous citric acid solution (1 M). The organic layer was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated. The residue was purified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes) to afford N-cyclobutyl-N′-[1-(3-{1-ethyl-3-[4-(trifluoromethyl)phenoxy]-1H-pyrazol-5-yl}phenyl)-1-methylethyl]sulfamide (270 mg, 40%) as a white solid. Calcd (M+1)+: 523.2. Found: 523.1. 1H NMR (600 MHz, cdcl3) δ 7.60-7.49 (m, 4H), 7.42 (t, J=7.7, 1H), 7.29 (d, J=7.6, 1H), 7.23 (d, J=8.7, 2H), 5.86 (s, 1H), 4.75 (s, 1H), 4.33 (d, J=8.5, 1H), 4.08 (q, J=7.2, 3H), 2.24 (dd, J=16.8, 7.8, 2H), 1.89-1.80 (m, 3H), 1.72 (s, 6H), 1.70-1.54 (m, 3H), 1.41 (t, J=7.2, 3H).

Workup

  1. temperaturecooling bath
  2. customwas removed
  3. stirringStirred an additional 20 minutes
  4. custompartitioned between dichloromethane and aqueous citric acid solution (1 M)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationThe dried solution was filtered
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-3bcc1867dbca4e6a91f331647da9b83a
Source dataset
uspto-grants-2014_10
Patent number
US08871796B2

Reaction notes

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