Cesium carbonate → [1-(2-Fluoro-4-{1-oxo-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-1H-isoquinolin-2-yl}-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

HRID 69493노트

반응식

HRID 69493 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH2:19][C@H:20]4[CH2:24][CH2:23][CH2:22][O:21]4)[CH:14]=3)[C:9]2=[O:25])=[CH:4][C:3]=1[F:26].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:79]([O:83][C:84](=[O:91])[NH:85][CH:86]1[CH2:90][CH2:89][NH:88][CH2:87]1)([CH3:82])([CH3:81])[CH3:80]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:79]([O:83][C:84](=[O:91])[NH:85][CH:86]1[CH2:90][CH2:89][N:88]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH:17]=[CH:16][C:15]4[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH2:19][C@H:20]5[CH2:24][CH2:23][CH2:22][O:21]5)[CH:14]=4)[C:9]3=[O:25])=[CH:4][C:3]=2[F:26])[CH2:87]1)([CH3:82])([CH3:80])[CH3:81]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 689912162-(4-Bromo-3-fluorophenyl)-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-2H-isoquinolin-1-one

생성물 1

HCID 68993565[1-(2-Fluoro-4-{1-oxo-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-1H-isoquinolin-2-yl}-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

A mixture of 2-(4-bromo-3-fluorophenyl)-6-[(R)-1-(tetrahydrofuran-2-yl)methoxy]-2H-isoquinolin-1-one (75 mg), palladium(II) acetate (3 mg), BINAP (14 mg), cesium carbonate (82 mg) and pyrrolidin-3-yl-carbamic acid tert-butyl ester (48 mg) in degassed toluene (2 mL) was stirred for 18 h at 100° C. The mixture was diluted with ethyl acetate, filtered and the filtrate was concentrated. The residue was purified by preparative HPLC. In this way the product was obtained with molecular weight 523.61 (C29H34FN3O5); MS (ESI): 524 (M+H+).

후처리

  1. filtrationfiltered
  2. concentrationthe filtrate was concentrated
  3. customThe residue was purified by preparative HPLC
  4. customIn this way the product was obtained with molecular weight 523.61 (C29H34FN3O5)

출처 및 근거

ORD 기록
ord-e95394959a81428e9a7a7fe1aab49321
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822495B2

반응 노트

불러오는 중…