1-Hydroxybenzotriazole → N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)-5-(3-chlorophenyl)-2-furamide

HRID 2114151Notes

Reaction equation

HRID 2114151 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.[Cl:22][C:23]1[CH:24]=[C:25]([C:29]2[O:33][C:32]([C:34](O)=[O:35])=[CH:31][CH:30]=2)[CH:26]=[CH:27][CH:28]=1.Cl.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[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:34]([C:32]4[O:33][C:29]([C:25]5[CH:26]=[CH:27][CH:28]=[C:23]([Cl:22])[CH:24]=5)=[CH:30][CH:31]=4)=[O:35])[CH:7]=3)=[CH:9][CH:10]=2)=[O:15])[CH2:20][CH2:19]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7362565-(3-Chlorophenyl)furan-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 113004885'-amino-N-(cyclopropylmethyl)-2'-methyl-1,1'-biphenyl-4-carboxamide

Product 1

HCID 11397578N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)-5-(3-chlorophenyl)-2-furamideYield 95.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5′-Amino-N-(cyclopropylmethyl)-2′-methyl-1,1′-biphenyl-4-carboxamide (24 mg, 0.085 mmol), 5-(3-chlorophenyl)-2-furoic acid (9.5 mg, 0.043 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (16 mg, 0.085 mmol), HOBT (12 mg, 0.085 mmol) and DIPEA (15 μl, 0.085 mmol) in DMF (4 ml) were stirred at room temperature for 4 h. The DMF was evaporated under vacuum and the residue partitioned between ethyl acetate and water. The organic fraction was concentrated under vacuum and the residue purfied by preparative HPLC to give N-(4′-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1′-biphenyl-3-yl)-5-(3-chlorophenyl)-2-furamide (20 mg, 95%). NMR; δH [2H6]—DMSO 10.25,(1H, s), 8.64,(1H, t), 8.11,(1H, t), 7.96-7.94,(3H, m), 7.75,(1H, dd), 7.66,(1H, d), 7.52,(1H, t), 7.49-7.44,(3H, m), 7.39,(1H, d), 7.34-7.31,(2H, m), 3.18,(2H, t), 2.23,(3H, s), 1.06,(1H, m), 0.45,(2H, m), 0.26,(2H, m). LCMS: retention time 3.88 min, MH+485.

Workup

  1. customThe DMF was evaporated under vacuum
  2. customthe residue partitioned between ethyl acetate and water
  3. concentrationThe organic fraction was concentrated under vacuum

Sources & evidence

ORD record
ord-53f174e01afe495f9c5021724ae51ce1
Source dataset
uspto-grants-2008_10
Patent number
US07432289B2

Reaction notes

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