Tetrahydrofuran → N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-Dicarboxamide

HRID 84493

반응식

HRID 84493 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]([N:27]5[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]5)=[O:26])=[CH:21][C:20]=4[Cl:34])[CH3:18])=[O:16])=[CH:14][C:10]=3[CH2:9][CH2:8][O:7][C:6]=2[CH:35]=1.[N:36]12[CH2:46]CCN=C1CCCC[CH2:37]2.[O:47]1CCCC1>CN.CCOC(C)=O.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC1C(P(C2C([CH2-])=CC=CC=2)C2C(C)=CC=CC=2)=CC=CC=1.CC(O)=O.CC(O)=O.[Pd].[Pd]>[Cl:34][C:20]1[CH:21]=[C:22]([C:25]([N:27]2[CH2:32][CH2:31][N:30]([CH3:33])[CH2:29][CH2:28]2)=[O:26])[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:37]([NH:36][CH3:46])=[O:47])=[CH:35][C:6]=3[O:7][CH2:8][CH2:9][C:10]=2[CH:14]=1)=[O:16]

참가 물질

8

반응물 3

HCID 8028Tetrahydrofuran2회HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 568343698-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide

생성물 1

HCID 44242776N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-Dicarboxamide수율 32%

시약·촉매·용매 4

HCID 98885Molybdenum carbonyl (Mo(CO)6)촉매HCID 11104995trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)촉매HCID 6329Methylamine용매HCID 8857Ethyl Acetate용매

반응 조건

온도
150 °C

실험 절차

To a solution containing 8-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (0.075 g, 0.13 mmol) in tetrahydrofuran (1.50 mL, 18.5 mmol), 2.00 M of methylamine in tetrahydrofuran (0.196 mL) was added molybdenumhexacarbonyl (34.4 mg, 0.130 mmol), trans-di(mu-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium (II) (18.3 mg, 0.0196 mmol) then 1,8-diazabicyclo[5.4.0]undec-7-ene (9.75 uL, 0.0652 mmol) and capped quickly to prevent CO gas from escaping. The reaction mixture was heated in a microwave at 150° C. for 20 min. The reaction mixture was diluted with EtOAc then filtered thru celite. The combined organics were dried (Na2SO4), filtered and concentrated. The crude was submitted for RP HPLC to give 181 (yield 32%). MS: (ESI+) 553.2

후처리

  1. filtrationthen filtered thru celite
  2. dry with materialThe combined organics were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated

출처 및 근거

ORD 기록
ord-8309b2d57e7d4087b4811b7d5ede439e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846762B2

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