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

HRID 627938
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HRID 627938 반응식
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]
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참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 167845
palladium(II) acetate
촉매
HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)촉매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c471105527f2483d9ad82b05fdd8170b
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09309265B2

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