2-Chlorobenzoic Acid → 5-n-Butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]-3-fluorobiphenyl-4-yl]methyl]-2-[2-chloro-5-(propionylamino)-phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 36292Notes

Reaction equation

HRID 36292 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[S:36](=[O:39])(=[O:38])[NH2:37])=[CH:26][C:25]=2[F:40])[C:7](=[O:22])[N:8]([C:10]2[CH:15]=[C:14]([NH:16][C:17](=[O:20])[CH2:18][CH3:19])[CH:13]=[CH:12][C:11]=2[Cl:21])[N:9]=1)[CH2:2][CH2:3][CH3:4].[Cl:41][C:42]1[CH:50]=[CH:49][CH:48]=[CH:47][C:43]=1[C:44](O)=[O:45].C1N=CN(C(N2C=NC=C2)=O)C=1.C1CCN2C(=NCCC2)CC1>>[CH2:1]([C:5]1[N:6]([CH2:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[S:36](=[O:38])(=[O:39])[NH:37][C:44](=[O:45])[C:43]3[CH:47]=[CH:48][CH:49]=[CH:50][C:42]=3[Cl:41])=[CH:26][C:25]=2[F:40])[C:7](=[O:22])[N:8]([C:10]2[CH:15]=[C:14]([NH:16][C:17](=[O:20])[CH2:18][CH3:19])[CH:13]=[CH:12][C:11]=2[Cl:21])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 4

HCID 83742-Chlorobenzoic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 103483205-n-Butyl-2-[2-chloro-5-(propionylamino)-phenyl]-2,4-dihydro-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-3H-1,2,4-triazol-3-one

Product 1

HCID 100328205-n-Butyl-4-[[2'-[N-(2-chlorobenzoyl)sulfamoyl]-3-fluorobiphenyl-4-yl]methyl]-2-[2-chloro-5-(propionylamino)-phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 65%

Procedure

Following the procedure of Example 51, 5-n-butyl-2-[2-chloro-5-(propionylamino)phenyl]-2,4-dihydro-4-[(3-fluoro-2'-sulfamoylbiphenyl-4-yl)methyl]-3H-1,2,4-triazol-3-one (from Step E) was reacted with 2-chlorobenzoic acid (2 equivalents), CDI (2 equiv), and DBU (2 equiv). Purification of the crude product by flash chromatography on silica gel (gradient elution with 1-5% MeOH in CH2Cl2) gave a 65% yield of the title compound as a white solid, mp >152° C. (gradual); homogeneous by TLC in 95:5 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 762 (M+K)+.

Workup

  1. customPurification of the crude product by flash chromatography on silica gel (gradient elution with 1-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9122465ffe244fae8a26b4332160440f
Source dataset
uspto-grants-1995_05
Patent number
US05411980

Reaction notes

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