Piperazine → (3aR,6aR)-5-Methyl-1-(4-piperazin-1-yl-phenyl)-octahydro-pyrrolo[3,4-b]pyrrole

HRID 12972

반응식

HRID 12972 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][CH2:11][C@@H:10]3[CH2:13][N:14]([CH3:16])[CH2:15][C@H:9]23)=[CH:4][CH:3]=1.[NH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:16][N:14]1[CH2:13][C@@H:10]2[C@@H:9]([N:8]([C:5]3[CH:6]=[CH:7][C:2]([N:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)=[CH:3][CH:4]=3)[CH2:12][CH2:11]2)[CH2:15]1

참가 물질

8

반응물 4

HCID 4837PiperazineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 44221503(3aR,6aR)-1-(4-Bromophenyl)-5-methyloctahydropyrrolo[3,4-b]pyrrole

생성물 1

HCID 68497954(3aR,6aR)-5-Methyl-1-(4-piperazin-1-yl-phenyl)-octahydro-pyrrolo[3,4-b]pyrrole

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
140 °C

실험 절차

The product of Example 72B (200 mg, 0.71 mmole), piperazine (200 mg, 2.33 mmole), tris(dibenzylideneacetone)dipalladium (20 mg, 0.022 mmole), (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (28 mg, 0.045 mmole), sodium tert-butoxide (140 mg, 1.46 mmole) and 7 ml of toluene were mixed under N2 in a Emrys process vial. The vial was sealed heated in the microwave for 15 minutes at 140° C. using the Emrys Creator. The mixture was diluted with water and extracted with dichloromethane (4×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product which was purified by column chromatography (10% methanol and 1% ammonium hydroxide in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 6.84-6.94 (m, 2H) 6.53-6.60 (m, 2H) 4.00-4.07 (m, 1H) 3.44-3.51(m, 1H) 3.11-3.20 (m, 1H) 2.99-3.09 (m, 9H) 2.88-2.96 (m, 1H) 2.68 (dd, J=9.66, 2.54 Hz, 1H) 2.48-2.59 (m, 2H), 2.31(s, 3H) 2.09-2.19 (m, 1H) 1.89 (m, 1H). MS-(M+H)+=287.

후처리

  1. customThe vial was sealed
  2. extractionextracted with dichloromethane (4×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product which
  8. customwas purified by column chromatography (10% methanol and 1% ammonium hydroxide in dichloromethane)

출처 및 근거

ORD 기록
ord-5096d94f2d7c4e03973ee5d92679950c
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728031B2

연결된 노트

불러오는 중…