3-Chloropyridin-4-amine → N-(3-chloropyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

HRID 627919

Reaction equation

HRID 627919 reaction equation
[S:1]1[C:5]2[C:6]3[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=3[O:8][CH2:9][CH2:10][C:4]=2[CH:3]=[C:2]1[C:15](Cl)=[O:16].[NH2:18][C:19]1[CH:24]=[CH:23][N:22]=[CH:21][C:20]=1[Cl:25]>>[Cl:25][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][C:19]=1[NH:18][C:15]([C:2]1[S:1][C:5]2[C:6]3[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=3[O:8][CH2:9][CH2:10][C:4]=2[CH:3]=1)=[O:16]

Participants

3

Reactant 2

HCID 5818533-Chloropyridin-4-amineHCID 579001474,5-Dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbonylchloride

Product 1

HCID 57900146N-(3-chloropyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

Procedure

Following Example 17, 4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carbonylchloride and 4-amino-3-chloropyridine were reacted to give N-(3-chloropyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide. To a solution of N-(3-chloropyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (0.340 g, 0.953 mmol) in DMF (5 mL, 60 mmol) was added sodium hydride (0.0381 g, 0.953 mmol). The reaction mixture was stirred at room temperature for about 10 min. followed by the addition of methyl iodide (65.25 uL, 1.048 mmol) and stirred at room temperature for another 1 hr. An aliquot was analyzed by LC/MS showing clean conversion to desired product. The reaction mix was diluted with EtOAc and washed with water/saline, dried (Na2SO4) then concentrated to a residue which was analyzed by LC/MS and 1H NMR. The crude product was taken into DMF at about 100 mg/mL, but was not totally soluble. Soluble material was purified by preparative RP-HPLC to give 184 (yield 30% of theoretical). MS: (ESI+) 372.2

Workup

  1. customwere reacted

Sources & evidence

ORD record
ord-639ce96ce1444cb79bdcb02cd5a8f720
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Linked notes

Loading…