5-Bromonicotinic acid → 5-bromo-N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl1,1'-biphenyl-3-yl)nicotinamide

HRID 2114131Notes

Reaction equation

HRID 2114131 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.[Br:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([CH:31]=1)[C:28](O)=[O:29]>C1COCC1>[Br:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([CH:31]=1)[C:28]([NH:1][C:2]1[CH:7]=[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)[C:5]([CH3:21])=[CH:4][CH:3]=1)=[O:29]

Participants

4

Reactant 2

HCID 887075-Bromonicotinic acidHCID 113004885'-amino-N-(cyclopropylmethyl)-2'-methyl-1,1'-biphenyl-4-carboxamide

Product 1

HCID 692019075-bromo-N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl1,1'-biphenyl-3-yl)nicotinamideYield 885.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5′-Amino-N-(cyclopropylmethyl)-2′-methyl-1,1′-biphenyl-4-carboxamide (26.4 mg, 0.009 mmol) and 5-bromonicotinic acid (38 mg, 0.18 mmol) were mixed in THF (2 ml) and the mixture shaken in a varian tube for 5 min at room temperature. Carbodiimde resin (250 mg, 0.27 mmol) was added and shaking continued for 72 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 then 1:1) and the solvent evaporated under vacuum to give 5-bromo-N-(4′-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl1,1′-biphenyl-3-yl)nicotinamide (37 mg, 85%). NMR; δH [2H6]—DMSO 10.50,(1H, s), 9.05,(1H, m), 8.90,(1H, m), 8.62,(1H, t), 8.54,(1H, t), 7.93,(2H, d), 7.70,(1H, dd), 7.66,(1H, d), 7.44,(2H, d), 7.31,(1H, d), 3.16,(2H, t), 2.21,(3H, s), 1.04,(1H, m), 0.43,(2H, m). LCMS: retention time 3.44 min, MH+464/466.

Workup

  1. stirringshaking
  2. waitcontinued for 72 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. custom1:1) and the solvent evaporated under vacuum

Sources & evidence

ORD record
ord-a311f5a974984aef9bb4483c63933cce
Source dataset
uspto-grants-2008_10
Patent number
US07432289B2

Reaction notes

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