Triethylamine → 2-(4-Fluorophenyl)-5-(5-(1-(5-fluoropyrimidin-2-yl)-cyclopropylcarbamoyl)-2-methylphenyl)-N-methylbenzofuran-3-carboxamide

HRID 1688354Notes

Reaction equation

HRID 1688354 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](O)=[O:25])=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.[F:31][C:32]1[CH:33]=[N:34][C:35]([C:38]2([NH2:41])[CH2:40][CH2:39]2)=[N:36][CH:37]=1.C(N(CC)CC)C>CN(C=O)C>[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]([C:24](=[O:25])[NH:41][C:38]5([C:35]6[N:36]=[CH:37][C:32]([F:31])=[CH:33][N:34]=6)[CH2:40][CH2:39]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:4][CH:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 592756533-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acidHCID 672913621-(5-Fluoropyrimidin-2-yl)cyclopropanamine

Product 1

HCID 595051792-(4-Fluorophenyl)-5-(5-(1-(5-fluoropyrimidin-2-yl)-cyclopropylcarbamoyl)-2-methylphenyl)-N-methylbenzofuran-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-4-methylbenzoic acid (0.04 g, 0.099 mmol, 1 eq), 1-(5-fluoropyrimidin-2-yl)cyclopropanamine (125 mg, crude), Py-Bop (0.067 g, 0.13 mmol, 1.3 eq) in DMF at ambient temperature under nitrogen was added triethylamine (0.026 g, 0.3 mmol, 3 eq). The clear mixture was stirred at ambient temperature for 12 h. The mixture was concentrated, diluted with water and extracted with EtOAc. The organic layer was further washed with water, dried over sodium sulphate and concentrated. The product obtained was purified by preparative TLC (Eluent Chloroform:Methanol 9.5:0.5 200 ml. Yield: 32 mg (55%). 1H NMR (400 MHz, CD3OD): δ 8.58 (d, J=0.5 Hz, 2H), 8.05-7.93 (m, 2H), 7.89-7.79 (m, 2H), 7.68 (s, 2H), 7.49-7.36 (m, 2H), 7.34-7.23 (m, 2H), 2.96 (s, 3H), 2.36 (s, 3H), 1.83-1.68 (m, 2H), 1.55-1.38 (m, 2H). LCMS: (ES+) m/z=539.2 (M+H)+

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was further washed with water
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe product obtained
  8. customwas purified by preparative TLC (Eluent Chloroform:Methanol 9.5:0.5 200 ml

Sources & evidence

ORD record
ord-9ea054bd2f734324992d8be93bab2a5a
Source dataset
uspto-grants-2012_04
Patent number
US08148382B2

Reaction notes

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