Cesium carbonate → (3aR,6aR)-ethyl 1-(4'-(6-oxopyridazin-1(6H)-yl)biphenyl-4-yl)hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate

HRID 12980

反応式

HRID 12980 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[C:19](=[O:20])[CH:18]=[CH:17][CH:16]=[N:15]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:69]1[CH2:73][CH2:72][C@@H:71]2[CH2:74][N:75]([C:77]([O:79][CH2:80][CH3:81])=[O:78])[CH2:76][C@H:70]12>C1COCC1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:20]=[C:19]1[N:14]([C:11]2[CH:12]=[CH:13][C:8]([C:5]3[CH:6]=[CH:7][C:2]([N:69]4[CH2:73][CH2:72][C@@H:71]5[CH2:74][N:75]([C:77]([O:79][CH2:80][CH3:81])=[O:78])[CH2:76][C@H:70]45)=[CH:3][CH:4]=3)=[CH:9][CH:10]=2)[N:15]=[CH:16][CH:17]=[CH:18]1

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 24743918(3AR,6AR)-5-Ethoxycarbonyl-1H-hexahydropyrrolo[3,4-B]pyrroleHCID 684968382-(4'-Bromobiphenyl-4-yl)pyridazin-3(2H)-one

生成物 1

HCID 67396526(3aR,6aR)-ethyl 1-(4'-(6-oxopyridazin-1(6H)-yl)biphenyl-4-yl)hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
70 °C

実験手順

2-(4′-Bromobiphenyl-4-yl)pyridazin-3(2H)-one (1.92 g, 5.86 mmol), palladium(II) acetate (0.158 g, 0.234 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.407 g, 0.703 mmol) and cesium carbonate (3.06 g, 9.38 mmol) were suspended in 25 mL of THF. A solution of (3aR,6aR)-ethyl hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carboxylate in 10 mL of THF was added and the mixture was heated at 70° C. under N2 for 20 hours. The mixture was allowed to cool to ambient temperature, diluted with 70 mL of EtOAc, and filtered through a ¼ pad of Celite®. The Celite® pad was washed with an additional 70 mL of EtOAc and the filtrate was absorbed on silica gel and chromatographed (eluting with 0-40% EtOAc in DCM) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.91 (dd, J=3.7, 1.7 Hz, 1H), 7.64 (s, 4H), 7.53 (d, J=8.8 Hz, 2H), 7.25 (dd, J=9.8, 3.4 Hz, 1H), 7.07 (dd, J=9.5, 1.7 Hz, 1H), 6.64 (d, J=8.5 Hz, 2H), 4.20-4.32 (m, 1H), 4.12 (q, J=7.5 Hz, 2H), 3.70-3.81(m, 1H), 3.59-3.69 (m, 2H), 3.48-3.58 (m, 1H), 3.36-3.48 (m, 2H), 2.99-3.10 (m, 1H), 2.20 (ddd, J=13.0, 7.3 Hz, 1H), 1.95 (ddd, J=12.9, 6.4 Hz, 1H), 1.24 (t, J=7.1 Hz, 3H). MS (ESI+) m/z 431(M+H)+.

後処理

  1. temperatureto cool to ambient temperature
  2. filtrationfiltered through a ¼ pad of Celite®
  3. washThe Celite® pad was washed with an additional 70 mL of EtOAc
  4. customthe filtrate was absorbed on silica gel
  5. customchromatographed
  6. wash(eluting with 0-40% EtOAc in DCM)

出典と根拠

ORDレコード
ord-5e186b2ef4ce4237953f3f28fe4c8dc7
出典データセット
uspto-grants-2010_06
特許番号
US07728031B2

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