(2-Amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone → tert-Butyl 3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)carbamoyl)-azetidine-1-carboxylate

HRID 1772367Notes

Reaction equation

HRID 1772367 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]3([C:30](O)=[O:31])[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH2:33][C:34]1[S:35][C:36]([CH3:49])=[C:37]([CH3:48])[C:38]=1[C:39]([C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=1)=[O:40].Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]3([C:30](=[O:31])[NH:33][C:34]4[S:35][C:36]([CH3:49])=[C:37]([CH3:48])[C:38]=4[C:39](=[O:40])[C:41]4[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=4)[CH2:20][N:21]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:22]3)=[O:17])[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 719710(2-Amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanoneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 678143551-[(tert-butoxy)carbonyl]-3-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)azetidine-3-carboxylic acid

Product 1

HCID 86706928tert-Butyl 3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)carbamoyl)-azetidine-1-carboxylateYield 61.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(((9H-fluoren-9-yl)methoxy)carbonylamino)-1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (0.438 g, 0.999 mmol), and (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (0.241 g, 0.908 mmol) in DCM (20 mL) at 0° C. was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (EDC.HCl) (209 mg, 1.090 mmol). The reaction was warmed to rt and stirred overnight, before it was concentrated to dryness. The residue was purified by flash chromatography (hexane/EtOAc) to give tert-Butyl 3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-((3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)carbamoyl)-azetidine-1-carboxylate as an orange oil (382 mg). LRMS (M+Na)+: 708 m/z.

Workup

  1. concentrationwas concentrated to dryness
  2. customThe residue was purified by flash chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-f0c8892f3a24428daf3a9d971f368422
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

Loading…