Methanol → Methyl 2-((2-chloro-4-(dimethylcarbamoyl)phenyl)(methyl)-carbamoyl)-4,5-dihydrobenzo[b] thieno[2,3-d]oxepine-8-carboxylate

HRID 627938Notes

Reaction equation

HRID 627938 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[S:12][C:13]([C:15]([N:17]([C:19]4[CH:24]=[CH:23][C:22]([C:25](=[O:29])[N:26]([CH3:28])[CH3:27])=[CH:21][C:20]=4[Cl:30])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:31]=1.[CH3:32][OH:33].CN([CH:37]=[O:38])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:30][C:20]1[CH:21]=[C:22]([C:25](=[O:29])[N:26]([CH3:28])[CH3:27])[CH:23]=[CH:24][C:19]=1[N:17]([CH3:18])[C:15]([C:13]1[S:12][C:11]2[C:5]3[CH:4]=[CH:3][C:2]([C:32]([O:38][CH3:37])=[O:33])=[CH:31][C:6]=3[O:7][CH2:8][CH2:9][C:10]=2[CH:14]=1)=[O:16]

Participants

6

Reactant 3

HCID 887MethanolHCID 6228DimethylformamideHCID 568341588-bromo-N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

Product 1

HCID 56834268Methyl 2-((2-chloro-4-(dimethylcarbamoyl)phenyl)(methyl)-carbamoyl)-4,5-dihydrobenzo[b] thieno[2,3-d]oxepine-8-carboxylateYield 89%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Procedure

The mixture of 8-bromo-N-(2-chloro-4-(dimethylcarbamoyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (27.0 g, 51.9 mmol), dppf (23.20 g, 41.9 mmol), Pd(OAc)2 (5.8 g, 25.8 mmol), TEA (27 mL), in DMF (270 mL) and MeOH (400 mL) was stirred under CO (50 psi) atmosphere at 70° C. for 2 days. The reaction mixture was filtrated and the filtrate was concentrated. The crude product was purified by silica gel chromatography eluted with Hexanes: EtOAc=1:1 to give methyl 2-((2-chloro-4-(dimethylcarbamoyl)phenyl)(methyl)-carbamoyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carboxylate (23.00 g, 89%). ESI-MS: 499.1. 1H NMR (DMSO-d6, 400 MHz): δ7.74-7.69 (m, 2H, ArH), 7.58-7.47 (m, 4H, ArH), 6.79 (s, 1H, ═CH), 4.23 (t, J=4.8 Hz, 2H, CH2), 3.83 (s, 3H, CH3), 3.31 (s, 3H, CH3), 3.01 (br, 5H, CH2, CH3), 2.94 (s, 3H, CH3).

Workup

  1. filtrationThe reaction mixture was filtrated
  2. concentrationthe filtrate was concentrated
  3. customThe crude product was purified by silica gel chromatography
  4. washeluted with Hexanes

Sources & evidence

ORD record
ord-c471105527f2483d9ad82b05fdd8170b
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

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