Triethylamine → 5-(5-(1-(4,6-dimethylpyrimidin-2-yl)cyclopropylcarbamoyl)-4-methoxy-2-methylphenyl)-4-fluoro-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1688375Notes

Reaction equation

HRID 1688375 reaction equation
[F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27]([OH:29])=O.[CH3:34][C:35]1[CH:40]=[C:39]([CH3:41])[N:38]=[C:37]([C:42]2([NH2:45])[CH2:44][CH2:43]2)[N:36]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[CH3:41][C:39]1[CH:40]=[C:35]([CH3:34])[N:36]=[C:37]([C:42]2([NH:45][C:27]([C:26]3[C:25]([O:31][CH3:32])=[CH:24][C:23]([CH3:33])=[C:22]([C:3]4[CH:4]=[CH:5][C:6]5[O:10][C:9]([C:11]6[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=6)=[C:8]([C:18]([NH:19][CH3:20])=[O:21])[C:7]=5[C:2]=4[F:1])[CH:30]=3)=[O:29])[CH2:43][CH2:44]2)[N:38]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 552956881-(4,6-Dimethyl-2-pyrimidinyl)cyclopropanamineHCID 592754645-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl) 2-methoxy-4-methylbenzoic acid

Product 1

HCID 595051605-(5-(1-(4,6-dimethylpyrimidin-2-yl)cyclopropylcarbamoyl)-4-methoxy-2-methylphenyl)-4-fluoro-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (50 mg, 0.11 mmol), crude 1-(4,6-dimethylpyrimidin-2-yl)cyclopropanamine (100 mg) in 2 ml DMF at room temperature was added BOP (100 mg, 0.22 M, 2.0 eq.) and triethyl amine (0.046 ml 0.33 M, 3.0 eq.), and the mixture stirred overnight under an N2 atmosphere. The mixture was poured into crushed ice, and the solid precipitate was filtered and dried. The product obtained was further purified by preparative HPLC. Yield: 15 mg (24%) 1H NMR (400 MHz, CD3OD): δ 7.97-7.94 (m, 2H), 7.89 (s, 1H), 7.51 (d, J=8.5 Hz, 1H), 7.31-7.25 (m, 3H), 7.19 (s, 1H), 7.14 (s, 1H), 4.11 (s, 3H), 2.96 (s, 3H), 2.48 (s, 6H), 2.31 (s, 3H), 1.86-1.83 (m, 2H), 1.55-1.52 (m, 2H). 19F NMR (376.57 MHz, CD3OD) δ −77.40 (TFA), −112.33, −122.75 (CFCl3 as reference).

Workup

  1. additionThe mixture was poured
  2. custominto crushed ice
  3. filtrationthe solid precipitate was filtered
  4. customdried
  5. customThe product obtained
  6. customwas further purified by preparative HPLC

Sources & evidence

ORD record
ord-2d5241c1f27d477bb86c2f4c049759f5
Source dataset
uspto-grants-2012_04
Patent number
US08148382B2

Reaction notes

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