Ethyl oxoacetate → HCID 178472741, compound

HRID 402524Notes

Reaction equation

HRID 402524 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:18]=2[Cl:19])[C:15](=[O:20])[NH:14][CH:13]=[CH:12]3)[CH2:4][CH2:3]1.[CH2:21]([O:23][C:24](=[O:27])[CH:25]=O)[CH3:22].C([BH3-])#N.[Na+]>CO>[CH2:21]([O:23][C:24](=[O:27])[CH2:25][NH:1][C@H:2]1[CH2:3][CH2:4][C@@H:5]([O:8][C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][C:18]=2[Cl:19])[C:15](=[O:20])[NH:14][CH:13]=[CH:12]3)[CH2:6][CH2:7]1)[CH3:22]

Participants

5

Reactant 3

HCID 70211Ethyl oxoacetate2×HCID 5003444Sodium cyanoborohydrideHCID 178511690HCID 178511690, compound

Product 1

HCID 178472741HCID 178472741, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
60 °C

Procedure

300 mg (0.91 mmol) of 6-cis-(4-amino-cyclohexyloxy)-7-chloro-2H-isoquinolin-1-one (12) were dissolved in 20 ml of methanol and treated with 258 mg (1.14 mmol) glyoxylic acid ethyl ester following the general method for reductive amination reactions. To achieve complete conversion, additional 5.0 equivalents of glyoxylic acid ethyl ester and 0.5 equivalents sodium cyano borohydride were added portionwise over 34 h and the temperature was increased to 60° C. after 5 h reaction time until the reaction went to completion. After filtration, the reaction solution was evaporated. The residue was dissolved in dichloromethane, washed with 1 N NaOH and saturated NaCl-solution, dried over MgSO4 and evaporated. The so obtained crude product was used in the next reaction without further purification. Rt=0.81 min (Method C). Detected mass: 365.4 (M+H+, methyl ester, because methanol was used as solvent), 0.87 min. (Method C). Detected mass: 379.4 (M+H+, ethyl ester, title compound).

Workup

  1. additionwere added portionwise over 34 h
  2. customreaction time until the reaction
  3. filtrationAfter filtration
  4. customthe reaction solution was evaporated
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washwashed with 1 N NaOH and saturated NaCl-solution
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe so obtained crude product
  10. customwas used in the next reaction without further purification

Sources & evidence

ORD record
ord-989dd939e7fd47eb9feaaac0d188485f
Source dataset
uspto-grants-2014_06
Patent number
US08742116B2

Reaction notes

Loading…