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 69493Notes

Reaction equation

HRID 69493 reaction equation
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]

Participants

8

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-e95394959a81428e9a7a7fe1aab49321
Source dataset
uspto-grants-2014_09
Patent number
US08822495B2

Reaction notes

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