Trifluoroacetic acid → N-Cyclopropyl-3-fluoro-5-{2-(3-hydroxy-2,2-dimethylpropyl)-4-[(4-methyl-1,4-diazepan-1-yl)methyl]-1-oxo-1,2-dihydroisoquinolin-6-yl}-4-methylbenzamide

HRID 906407Notes

Reaction equation

HRID 906407 reaction equation
[CH:1]1([NH:4][C:5](=[O:33])[C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[C:18](=[O:22])[N:17]([CH2:23][C:24]([CH3:28])([CH3:27])[CH2:25][OH:26])[CH:16]=[C:15]4[CH:29]=O)[C:9]([CH3:31])=[C:8]([F:32])[CH:7]=2)[CH2:3][CH2:2]1.[CH3:34][N:35]1[CH2:41][CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(C(F)(F)F)=O>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH:1]1([NH:4][C:5](=[O:33])[C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[C:18](=[O:22])[N:17]([CH2:23][C:24]([CH3:27])([CH3:28])[CH2:25][OH:26])[CH:16]=[C:15]4[CH2:29][N:38]3[CH2:39][CH2:40][CH2:41][N:35]([CH3:34])[CH2:36][CH2:37]3)[C:9]([CH3:31])=[C:8]([F:32])[CH:7]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 2283491-MethylhomopiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 86640963N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

Product 1

HCID 59285293N-Cyclopropyl-3-fluoro-5-{2-(3-hydroxy-2,2-dimethylpropyl)-4-[(4-methyl-1,4-diazepan-1-yl)methyl]-1-oxo-1,2-dihydroisoquinolin-6-yl}-4-methylbenzamide

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Conditions

Temperature
20 °C

Procedure

To a mixture of N-cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide (Example 2c, 0.20 g) and titanium(IV) isopropoxide (2 mL) was added 1-methyl-1,4-diazepane (0.17 mL) under nitrogen. The resulting mixture was stirred at 20° C. for 2 h before adding sodium triacetoxyborohydride (0.38 g). The mixture was stirred at room temperature for 2 h. TFA (5 mL) was added and the mixture stirred at room temperature for 72 h and then evaporated to dryness. The mixture was quenched with 10% aq ammonia (5 ml) and extracted with ethyl acetate. The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified by preparative HPLC (Phenomenex Gemini column using a 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as eluent) to afford the title compound (0.055 g) as a white solid.

Workup

  1. stirringThe mixture was stirred at room temperature for 2 h
  2. stirringthe mixture stirred at room temperature for 72 h
  3. customevaporated to dryness
  4. customThe mixture was quenched with 10% aq ammonia (5 ml)
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic was dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by preparative HPLC (Phenomenex Gemini column

Sources & evidence

ORD record
ord-e6452cc9dc664b428674b8002894718f
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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