Trifluoroacetic acid → 2-Amino-8-fluoro-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide

HRID 884747Notes

Reaction equation

HRID 884747 reaction equation
C1([C@H](NC(C(C2C=CC=C(F)C=2C(O)=O)C(=O)C)=O)C2C=CC=C(F)C=2)CCC1.C(OC(C)(C)C)(=O)NN.C(OC(=O)[NH:45][N:46]1[C:55]([CH3:56])=[C:54]([C:57](=[O:71])[NH:58][C@@H:59]([CH:67]2[CH2:70][CH2:69][CH2:68]2)[C:60]2[CH:65]=[CH:64][CH:63]=[C:62]([F:66])[CH:61]=2)[C:53]2[C:48](=[C:49]([F:72])[CH:50]=[CH:51][CH:52]=2)[C:47]1=[O:73])(C)(C)C.C(O)(C(F)(F)F)=O>C1C=CC=CC=1.ClCCCl>[CH:67]1([C@H:59]([NH:58][C:57]([C:54]2[C:53]3[C:48](=[C:49]([F:72])[CH:50]=[CH:51][CH:52]=3)[C:47](=[O:73])[N:46]([NH2:45])[C:55]=2[CH3:56])=[O:71])[C:60]2[CH:65]=[CH:64][CH:63]=[C:62]([F:66])[CH:61]=2)[CH2:70][CH2:69][CH2:68]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 70091tert-Butyl carbazateHCID 577333962-(1-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-2-oxo-propyl)-6-fluoro-benzoic acidHCID 67297917(4-{[(S)-Cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-8-fluoro-3-methyl-1-oxo-1H-isoquinolin-2-yl)-carbamic acid tert-butyl ester

Product 1

HCID 592530752-Amino-8-fluoro-3-methyl-1-oxo-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-amide

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 241BenzeneSolvent

Procedure

A solution of 2-(1-{[(S)-cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-2-oxo-propyl)-6-fluoro-benzoic acid (2.148 g, 5.351 mmol) and tert-butyl carbazate (1.628 g, 12.32 mmol) in benzene (100 mL) was stirred under reflux for 20 hours. LC-MS indicated the formation of (4-{[(S)-Cyclobutyl-(3-fluoro-phenyl)-methyl]-carbamoyl}-8-fluoro-3-methyl-1-oxo-1H-isoquinolin-2-yl)-carbamic acid tert-butyl ester (tR=1.54, UV 39%, ELSD 80%, m/z 398.4 (major), 442.5, 498.7 (MH+)). The reaction mixture was rotovaped. The residue was dissolved in 1,2-dichloroethane (15 ml) and TFA (15 ml) was added. After 60 min it was evaporated, partitioned between sat. aq. NaHCO3 and ethyl acetate, evaporated to give a crude residue of the title compound (1.7 g) that was used in the next step without purification. LC-MS (m/z) 398.0 (MH+), tR=1.24.

Workup

  1. temperatureunder reflux for 20 hours
  2. customAfter 60 min it was evaporated
  3. custompartitioned between sat. aq. NaHCO3 and ethyl acetate
  4. customevaporated

Sources & evidence

ORD record
ord-ab89a172da954d1f949672394a7c36ad
Source dataset
uspto-grants-2012_08
Patent number
US08242134B2

Reaction notes

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