1,2-Dichloroethane → 3-[[2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-1,3,4-benzotriazepin-3-yl]acetyl]amino]-N-methylsulfonylbenzamide

HRID 2113312Notes

Reaction equation

HRID 2113312 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].[CH:6]1([C:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]([CH2:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])[C:15](=[O:30])[N:14]([CH2:31][C:32]([NH:34][C:35]3[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=3)[C:38](O)=[O:39])=[O:33])[N:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH:6]1([C:12]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[N:16]([CH2:23][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])[C:15](=[O:30])[N:14]([CH2:31][C:32]([NH:34][C:35]3[CH:43]=[CH:42][CH:41]=[C:37]([C:38]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[O:39])[CH:36]=3)=[O:33])[N:13]=2)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 72879MethanesulfonamideHCID 115277383-{2-[5-Cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetylamino}-benzoic Acid

Product 1

HCID 167330513-[[2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-1,3,4-benzotriazepin-3-yl]acetyl]amino]-N-methylsulfonylbenzamideYield 83%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Methanesulfonamide (96 mg, 1.00 mmol) was added to a solution of 3-{2-[5-cyclohexyl-1-(3,3-dimethyl-2-oxo-butyl)-2-oxo-1,2-dihydro-3H-1,3,4-benzotriazepin-3-yl]-acetylamino}-benzoic acid (Example 2)(409 mg, 0.80 mmol), EDC (207 mg, 1.08 mmol) and DMAP (122 mg, 1.00 mmol) in DCM (20 ml) at room temperature. After stirring for 17 h, the mixture was washed with 5% KHSO4 (50 ml), brine (50 ml) and dried (MgSO4). Filtration and evaporation of the solvent gave the crude product which was purified by flash column chromatography (MeOH-DCM (1:10) to afford the title compound as a white crystalline solid (392 mg, 83%). 1H NMR (DMSO-d6) 9.99 (1H, s), 8.02 (1H, s), 7.63-7.36 (5H, m), 7.23 (1H, t), 7.13 (1H, d), 4.73 (2H, dd), 4.29 and 4.25 (2H, d×2), 3.24 (3H, s), 2.87 (1H, m), 1.80-1.48 (6H, m), 1.30-1.09 (13H, m). The compound was further characterised as the N-methyl-D-glucamine salt. Found: C, 53.93; H, 7.07; N, 10.17%; C30H37N5O6S.C7H17NO5.2.0H2O requires: C, 53.74; H, 7.07; N, 10.16%.

Workup

  1. washthe mixture was washed with 5% KHSO4 (50 ml), brine (50 ml)
  2. dry with materialdried (MgSO4)
  3. filtrationFiltration and evaporation of the solvent
  4. customgave the crude product which
  5. customwas purified by flash column chromatography (MeOH-DCM (1:10)

Sources & evidence

ORD record
ord-3f1b051071ef40619d2222c2afa3eb65
Source dataset
uspto-grants-2009_04
Patent number
US07524837B2

Reaction notes

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