Water → tert-butyl 8-carbamoyl-6-chloro-7-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 589866

반응식

HRID 589866 반응식
Br[C:2]1[C:3]([C:19](=[O:21])[NH2:20])=[C:4]2[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][CH2:6][N:5]2[C:17]=1[Cl:18].[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.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.Cl[Pd]Cl.[Fe+2].ClCCl>[C:19]([C:3]1[C:2]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:17]([Cl:18])[N:5]2[CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][C:4]=12)(=[O:21])[NH2:20]

참가 물질

8

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 66585083tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

생성물 1

HCID 66584861tert-butyl 8-carbamoyl-6-chloro-7-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate수율 40%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
100 °C

실험 절차

To a solution under nitrogen of 3.78 g (9.98 mmol) of tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in 160 ml of tetrahydrofuran are added 1.34 g (11.0 mmol) of benzeneboronic acid (CAS 98-80-6), 8 ml of water, 9.76 g (30.0 mmol) of caesium carbonate and 0.98 g (1.20 mmol) of a complex of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) and dichloromethane (PdCl2(dppf).CH2Cl2—CAS 95464-05-4). The mixture is stirred for 6 hours at 100° C. and then for 15 hours at 80° C., then cooled to room temperature and filtered through Celite™. The Celite is rinsed with 100 ml of ethyl acetate and 30 ml of water are added to the combined filtrates. The organic phase is separated out by settling, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue obtained is chromatographed on a column of silica gel, eluting with a mixture of 5 to 50% ethyl acetate in dichloromethane, to give 1.50 g of tert-butyl 8-carbamoyl-6-chloro-7-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in the form of a white solid after recrystallization from ethyl acetate and drying at 60° C. under reduced pressure.

후처리

  1. waitfor 15 hours at 80° C.
  2. temperaturecooled to room temperature
  3. filtrationfiltered through Celite™
  4. washThe Celite is rinsed with 100 ml of ethyl acetate and 30 ml of water
  5. additionare added to the combined filtrates
  6. customThe organic phase is separated out
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue obtained
  11. customis chromatographed on a column of silica gel
  12. washeluting with a mixture of 5 to 50% ethyl acetate in dichloromethane

출처 및 근거

ORD 기록
ord-cbf55187fc2a44b1971d5c46724696d4
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233965B2

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