2-Bromothiazole → (3aR,6aR)-5-methyl-1-{4-[4-(1,3-thiazol-2-yl)piperazin-1-yl]phenyl}octahydropyrrolo[3,4-b]pyrrole

HRID 12965

반응식

HRID 12965 반응식
[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]4)=[CH:12][CH:11]=3)[CH2:6][CH2:7]2)[CH2:3]1.Br[C:23]1[S:24][CH:25]=[CH:26][N:27]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.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]>[CH3:1][N:2]1[CH2:9][C@@H:8]2[C@@H:4]([N:5]([C:10]3[CH:11]=[CH:12][C:13]([N:16]4[CH2:17][CH2:18][N:19]([C:23]5[S:24][CH:25]=[CH:26][N:27]=5)[CH2:20][CH2:21]4)=[CH:14][CH:15]=3)[CH2:6][CH2:7]2)[CH2:3]1

참가 물질

8

반응물 4

HCID 764302-BromothiazoleHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68497954(3aR,6aR)-5-Methyl-1-(4-piperazin-1-yl-phenyl)-octahydro-pyrrolo[3,4-b]pyrrole

생성물 1

HCID 24743687(3aR,6aR)-5-methyl-1-{4-[4-(1,3-thiazol-2-yl)piperazin-1-yl]phenyl}octahydropyrrolo[3,4-b]pyrrole

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

반응 조건

온도
80 °C

실험 절차

The product of Example 49B (50 mg, 0.175 mmole), 2-bromothiazole (35 mg, 0.21 mmole), tris(dibenzylideneacetone)dipalladium (3.2 mg, 0.0035 mmole), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4.4 mg, 0.007 mmole) and sodium tert-butoxide (25.2 mg, 1.5 mmole) were dissolved in 1 ml of toluene and heated at 80° C. under N2 for 24 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane (5×). The combined organics were dried over sodium sulfate, filtered, concentrated under reduced pressure and was purified by chromatography (eluting with a mixture of 5% methanol in dichloromethane) to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.22 (d, J=3.73 Hz, 1H) 6.88-6.96 (m, 2H) 6.59 (d, J=3.73 Hz, 1H) 6.50-6.58 (m, 2H) 4.06-4.22 (m, 1H) 3.60-3.69 (m, 4H) 3.48-3.58 (m, 1H) 3.17-3.27 (m, 1H) 3.11-3.17 (m, 4H) 2.95-3.07 (m, 1H) 2.61-2.71 (m, 4H) 2.41(s, 3H) 2.10-2.22 (m, 1H) 1.93-1.97 (m, 1H); MS (M+H)+=370.

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with dichloromethane (5×)
  3. dry with materialThe combined organics were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customwas purified by chromatography (
  7. washeluting with a mixture of 5% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-ebbc514ea2a74512a57eb8c3dfc63b48
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07728031B2

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