1253955-17-7 → (R)-4-(3-((tert-butoxycarbonyl)amino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate

HRID 1944145Notes

Reaction equation

HRID 1944145 reaction equation
[CH3:1][C:2]1[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:3]=1[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH2:28][NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:15]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[CH:24]=[N:23][CH:22]=[CH:21]3)=[O:16])=[CH:10][CH:9]=1)=[O:5]>CO>[CH3:1][C:2]1[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:3]=1[C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C@@H:14]([CH2:28][NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:15]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[CH:24]=[N:23][CH:22]=[CH:21]3)=[O:16])=[CH:12][CH:13]=1)=[O:5].[CH3:1][C:2]1[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:3]=1[C:4]([O:6][CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C@H:14]([CH2:28][NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:15]([NH:17][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[CH:24]=[N:23][CH:22]=[CH:21]3)=[O:16])=[CH:12][CH:13]=1)=[O:5]

Participants

4

Reactant 1

HCID 595638051253955-17-7

Product 2

HCID 66613359(R)-4-(3-((tert-butoxycarbonyl)amino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoateHCID 66613838(S)-4-(3-((tert-butoxycarbonyl)amino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(S)-4-(3-(tert-butoxycarbonylamino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (E145-S) and (R)-4-(3-(tert-butoxycarbonylamino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (E145-R) were prepared from E145 according to the scheme in FIG. 10. 4-(3-(tert-butoxycarbonylamino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate was dissolve in methanol and the R and S enantiomers separated by supercritical fluid chromatography (Chiralpak AS-H column, eluent: 18.8% MeOH, 0.2% dimethylethylamine, 80% CO2). The enantiomers were then each purified by column chromotagraphy (SiO2, 0-5% MeOH/CH2Cl2gradient). The enantiomeric excess for each enantiomer was >98%.

Workup

  1. customthe R and S enantiomers separated by supercritical fluid chromatography (Chiralpak AS-H column, eluent: 18.8% MeOH, 0.2% dimethylethylamine, 80% CO2)
  2. customeach purified by column chromotagraphy (SiO2, 0-5% MeOH/CH2Cl2gradient)

Sources & evidence

ORD record
ord-117db81e6013455ba30db2efdc0b46a1
Source dataset
uspto-grants-2013_03
Patent number
US08394826B2

Reaction notes

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