Pyridine → 8-bromo-N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-4,5-dihydro-benzo[b]thieno[2,3-d]oxepine-2-carboxamide

HRID 84517

Reaction equation

HRID 84517 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([OH:17])=O)=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:18]=1.[NH2:19][C:20]1[CH:30]=[CH:29][C:23]([C:24]([N:26]([CH3:28])[CH3:27])=[O:25])=[CH:22][C:21]=1[Cl:31].N1C=CC=CC=1>O=S(Cl)Cl.C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([NH:19][C:20]4[CH:30]=[CH:29][C:23]([C:24](=[O:25])[N:26]([CH3:27])[CH3:28])=[CH:22][C:21]=4[Cl:31])=[O:17])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:18]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 202874814-Amino-3-chloro-N,N-dimethylbenzamideHCID 579001638-Bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxylic acid

Product 1

HCID 568341578-bromo-N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-4,5-dihydro-benzo[b]thieno[2,3-d]oxepine-2-carboxamideYield 77%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 8-bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxylic acid (25.00 g, 76.9 mmol) in SOCl2 (200 mL) was heated at 90-100° C. for 3 h. Concentration of the reaction mixture gave the crude acid chloride. A suspension of the acid chloride in THF (600 mL) was treated with a solution of 4-amino-3-chloro-N,N-dimethylbenzamide (18.23 g, 92.3 mmol) and pyridine (14 mL) in THF (200 mL) at 0° C. The mixture was allowed to reach room temperature and stirred overnight. After concentration, water (200 mL) was added into the mixture. The resulting precipitate was collected by filtration, washed with water and dried to give 8-bromo-N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-4,5-dihydro-benzo[b]thieno[2,3-d]oxepine-2-carboxamide (29.88 g, yield: 77%). ESI-MS: 504.99. 1H NMR (DMSO-d6, 400 MHz): δ10.14 (s, 1H, NH), 7.86 (s, 1H, ArH), 7.67-7.57 (m, 3H, ArH), 7.40-7.25 (m, 3H, ArH), 4.32 (t, J=5.2 Hz, 2H, CH2), 3.21 (t, J=5.2 Hz, 2H, CH2), 2.95 (s, 3H, CH3), 2.92 (s, 3H, CH3).

Workup

  1. customConcentration of the reaction mixture gave the crude acid chloride
  2. customto reach room temperature
  3. concentrationAfter concentration, water (200 mL)
  4. additionwas added into the mixture
  5. filtrationThe resulting precipitate was collected by filtration
  6. washwashed with water
  7. customdried

Sources & evidence

ORD record
ord-542e27bb7f59462aa2b7606a94207e9f
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Linked notes

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