1-Hydroxybenzotriazole → 2-(4-Fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(5-methylthiazol-2-yl)cyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide

HRID 1688336Notes

Reaction equation

HRID 1688336 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([CH:27]=[CH:28][C:29]=4[CH3:30])[C:24]([OH:26])=O)=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.[CH3:31][C:32]1[S:36][C:35]([C:37]2([NH2:40])[CH2:39][CH2:38]2)=[N:34][CH:33]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>ClCCl.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[CH:19][C:18]([C:21]4[CH:22]=[C:23]([C:24](=[O:26])[NH:40][C:37]5([C:35]6[S:36][C:32]([CH3:31])=[CH:33][N:34]=6)[CH2:39][CH2:38]5)[CH:27]=[CH:28][C:29]=4[CH3:30])=[CH:17][C:11]=3[C:12]=2[C:13]([NH:14][CH3:15])=[O:16])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 592756533-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 67210769HCID 67210769, compound

Product 1

HCID 595051302-(4-Fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(5-methylthiazol-2-yl)cyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.2 g, 0.5 mmol, 1 eq), 1-(5-methylthiazol-2-yl)cyclopropanamine (0.093 g, 0.6 mmol, 1.2 eq), EDCI.HCl (0.103 g, 0.54 mmol, 1.1 eq), HOBT (0.067 g, 0.5 mmol, 1.5 eq) and TEA (0.21 ml, 1.5 mmol, 3 eq) were dissolved in dichloromethane and the mixture was stirred at room temperature for 18 h. The mixture was then added with water, and the organic layer was separated and washed with water, and the product was purified by preparative TLC. Yield: 25 mg (15%). 1H NMR (400 MHz, DMSO-d6): δ 1.34-1.37 (m, 2H), 1.50-1.53 (m, 2H), 2.31 (s, 3H), 2.35 (s, 3H), 2.83-2.84 (d, J=4.8 Hz, 3H), 7.27 (d, J=1.2 Hz, 1H), 7.39-7.47 (m, 4H), 7.60 (d, J=1.6 Hz, 1H), 7.76-7.78 (d, J=8.4 Hz 1H), 7.83-7.85 (m, 2H), 8.02 (m, 2H), 8.45 (m, 1H), 9.51 (s, 1H) LCMS: (ES+) m/z=540 (M+H)+

Workup

  1. customthe organic layer was separated
  2. washwashed with water
  3. customthe product was purified by preparative TLC

Sources & evidence

ORD record
ord-253883de404a42709006d6eb5a004035
Source dataset
uspto-grants-2012_04
Patent number
US08148382B2

Reaction notes

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