5'-amino-N-(cyclopropylmethyl)-2'-methyl-1,1'-biphenyl-4-carboxamide → N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)-4-methoxy-3-phenylbenzamide

HRID 2114136Notes

Reaction equation

HRID 2114136 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:21])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:16][CH2:17][CH:18]3[CH2:20][CH2:19]3)=[O:15])=[CH:10][CH:9]=2)[CH:7]=1.[CH3:22][O:23][C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][C:25]=1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1>[CH:18]1([CH2:17][NH:16][C:14]([C:11]2[CH:12]=[CH:13][C:8]([C:6]3[C:5]([CH3:21])=[CH:4][CH:3]=[C:2]([NH:1][C:28](=[O:29])[C:27]4[CH:31]=[CH:32][C:24]([O:23][CH3:22])=[C:25]([C:33]5[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=5)[CH:26]=4)[CH:7]=3)=[CH:9][CH:10]=2)=[O:15])[CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 113004885'-amino-N-(cyclopropylmethyl)-2'-methyl-1,1'-biphenyl-4-carboxamideHCID 167688254-Methoxy-3-phenylbenzoic acid

Product 1

HCID 69201726N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)-4-methoxy-3-phenylbenzamideYield 48.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5′-Amino-N-(cyclopropylmethyl)-2′-methyl-1,1′-biphenyl-4-carboxamide (53 mg, 0.189 mmol) and 4-methoxy-3-phenylbenzoic acid (129 mg, 0.57mmol) were mixed in THF (5 ml) and the mixture shaken in a varian tube for 15 min at room temperature. Carbodiimde resin (500 mg) was added and shaking continued for 18 h. The solution was filtered off and concentrated under vacuum. The residue was chromatographed on a silica gel flash column eluting with ethyl acetate/hexane (1:2) and the solvent evaporated under vacuum to give N-(4′-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1′-biphenyl-3-yl)-4-methoxy-3-phenylbenzamide (45 mg). NMR; δH CDCl3 7.90, (1H, dd), 7.82-7.79,(4H, m), 7.58,(1H, dd), 7.53-7.33,(5H, m), 7.27-7.25,(1H, m), 7.05,(1H, d), 6.25,(1H, t), 3.87,(3H, s), 3.34,(2H, m), 2.22,(3H, s), 1.08,(1H, m), 0.57,(2H, m), 0.29,(2H, m). LCMS: retention time 3.78 min, MH+491.

Workup

  1. stirringshaking
  2. waitcontinued for 18 h
  3. filtrationThe solution was filtered off
  4. concentrationconcentrated under vacuum
  5. customThe residue was chromatographed on a silica gel flash column
  6. washeluting with ethyl acetate/hexane (1:2)
  7. customthe solvent evaporated under vacuum

Sources & evidence

ORD record
ord-e5b158f2ad9149d0ac27f631581a5fa1
Source dataset
uspto-grants-2008_10
Patent number
US07432289B2

Reaction notes

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