Triethylamine → HCID 86652732, compound

HRID 1895926Notes

Reaction equation

HRID 1895926 reaction equation
[C:1]([N:8]1[CH:12]=[CH:11]N=C1)([N:3]1C=CN=C1)=[O:2].[F:13][C:14]([F:34])([F:33])[O:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([N:25]2[CH2:30][CH2:29][CH:28]([O:31]N)[CH2:27][CH2:26]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1.[CH2:35](N(CC)CC)[CH3:36].C1(CN)CC1>C(Cl)Cl>[CH:11]1([CH2:12][NH:8][C:1]([NH:3][O:31][CH:28]2[CH2:29][CH2:30][N:25]([S:22]([C:19]3[CH:20]=[CH:21][C:16]([O:15][C:14]([F:34])([F:33])[F:13])=[CH:17][CH:18]=3)(=[O:24])=[O:23])[CH2:26][CH2:27]2)=[O:2])[CH2:36][CH2:35]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 75646CyclopropanemethanamineHCID 67118448HCID 67118448, compound

Product 1

HCID 86652732HCID 86652732, compoundYield 39.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1,1′-Carbonyldiimidazole (227 mg, 1.4 mmol) was added to a solution of O-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yl) hydroxylamine (238 mg, 0.70 mmol) and triethylamine (141 mg, 1.4 mmol) in CH2Cl2 (6 ml) and stirred at room temperature for 17 hours. Cyclopropylmethanamine (75 mg, 1.05 mmol) was added to the reaction mixture and stirred at room temperature for another 7 hours. The reaction mixture was quenched with H2O (10 ml) and aqueous 1 N HCl solution (pH=3) and extracted with CH2Cl2 (70 ml×3). The combined organic phase was washed with aqueous NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/n-hexane: 33/67) to give 1-(cyclopropylmethyl)-3-(1-(4-(trifluoromethoxy)phenylsulfonyl)piperidin-4-yloxy)urea (120 mg, 39%) as a white solid: LCMS: 438 [M+1]+. 1H NMR (DMSO-d6) δ: 0.14 (m, 2H), 0.35 (m, 2H), 0.90 (m, 1H), 1.74 (m, 2H), 1.86 (m, 2H), 2.85 (m, 4H), 3.20 (m, 2H), 3.65 (m, 1H), 6.71 (m, 1H), 7.65 (m, 2H), 7.90 (m, 2H), 8.86 (s, 1H).

Workup

  1. stirringstirred at room temperature for another 7 hours
  2. customThe reaction mixture was quenched with H2O (10 ml) and aqueous 1 N HCl solution (pH=3)
  3. extractionextracted with CH2Cl2 (70 ml×3)
  4. washThe combined organic phase was washed with aqueous NaHCO3 solution and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (ethyl acetate/n-hexane: 33/67)

Sources & evidence

ORD record
ord-9327160358de4f35b24fb368f26477ee
Source dataset
uspto-grants-2013_08
Patent number
US08518934B2

Reaction notes

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