Water → 1-([1,1'-biphenyl]-2-yl)-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzyl)urea

HRID 62054

Reaction equation

HRID 62054 reaction equation
[F:1][C:2]([F:28])([F:27])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21]C(N=[N+]=[N-])=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[C:29]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]([NH2:35])=[CH:31][CH:32]=[CH:33][CH:34]=1.[C:42](=[O:45])([O-])[O-].[Cs+].[Cs+].O.C(#[N:51])C>>[C:29]1([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[NH:35][C:42]([NH:51][CH2:21][C:18]1[CH:17]=[CH:16][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:8]=[CH:9][C:4]([O:3][C:2]([F:27])([F:28])[F:1])=[CH:5][CH:6]=3)[N:11]=2)=[CH:20][CH:19]=1)=[O:45]

Participants

6

Reactant 5

HCID 962WaterHCID 6342Acetonitrile2×HCID 70152-AminobiphenylHCID 10796Cesium carbonateHCID 904416662-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acetyl azide

Product 1

HCID 1186751111-([1,1'-biphenyl]-2-yl)-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzyl)ureaYield 28%

Procedure

A solution of 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acetyl azide (0.100 g, 0.258 mmol) in acetonitrile (1.25 mL) was heated to 80° C. for 2.5 hours. The resulting solution was cooled to room temperature and [1,1′-biphenyl]-2-amine (0.0479 g, 0.283 mmol) and cesium carbonate (0.0920 g, 0.283 mmol) were added as solids. An additional amount of acetonitrile (1.0 mL) was added and the reaction was allowed to stir for 18 hours at room temperature. The reaction mixture was poured into water (20 mL) and extracted with ethyl acetate (3×25 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified by flash chromatography using 0-80% ethyl acetate/B, where B=1:1 dichloromethane/hexanes to afford the title compound as a white solid (0.039 g, 28%): 1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 8.12-8.04 (m, 4H), 7.90 (dd, J=8.2, 1.2 Hz, 1H), 7.63 (dq, J=9.0, 0.9 Hz, 2H), 7.55-7.46 (m, 3H), 7.45-7.36 (m, 5H), 7.33-7.26 (m, 1H), 7.18 (dd, J=7.6, 1.7 Hz, 1H), 7.14-7.06 (m, 2H), 4.32 (d, J=5.8 Hz, 2H); 19F NMR (376 MHz, DMSO-d6) δ −56.96; ESIMS m/z 530 ([M+H]+).

Workup

  1. extractionextracted with ethyl acetate (3×25 mL)
  2. dry with materialThe combined organic layers were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-bb565127acc04a7f88d8f88e6acd1d6d
Source dataset
uspto-grants-2016_09
Patent number
US09445594B2

Linked notes

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