tert-Butyl ((S)-1-(((S)-3,3-dimethyl-1-((S)-7-nitro-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate → tert-Butyl ((S)-1-(((S)-1-((S)-7-amino-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 339255Notes

Reaction equation

HRID 339255 reaction equation
[CH3:1][C:2]([CH3:47])([CH3:46])[C@H:3]([NH:32][C:33](=[O:45])[C@@H:34]([N:36]([CH3:44])[C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])[CH3:35])[C:4]([N:6]1[C@H:15]([C:16](=[O:28])[NH:17][C@H:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][CH2:20][CH2:19]2)[CH2:14][C:13]2[C:8](=[CH:9][C:10]([N+:29]([O-])=O)=[CH:11][CH:12]=2)[CH2:7]1)=[O:5]>CO.[Pd]>[NH2:29][C:10]1[CH:9]=[C:8]2[C:13]([CH2:14][C@@H:15]([C:16](=[O:28])[NH:17][C@H:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH2:21][CH2:20][CH2:19]3)[N:6]([C:4](=[O:5])[C@@H:3]([NH:32][C:33](=[O:45])[C@@H:34]([N:36]([CH3:44])[C:37](=[O:43])[O:38][C:39]([CH3:41])([CH3:42])[CH3:40])[CH3:35])[C:2]([CH3:1])([CH3:46])[CH3:47])[CH2:7]2)=[CH:12][CH:11]=1

Participants

4

Reactant 1

HCID 86705892tert-Butyl ((S)-1-(((S)-3,3-dimethyl-1-((S)-7-nitro-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

Product 1

HCID 86705894tert-Butyl ((S)-1-(((S)-1-((S)-7-amino-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3,3-dimethyl-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamateYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a pressure flask containing 10% Pd/C (240 mg, 0.23 mmol) was added a solution of tert-butyl ((S)-1-(((S)-3,3-dimethyl-1-((S)-7-nitro-3-(((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-1-oxobutan-2-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (1.46 g, 2.25 mmol) in MeOH (11.2 mL). The resulting reaction mixture was stirred under H2 at 15 psi for 3 h and then filtered through a pad of CELITE® rinsing with EtOAc. The filtrate was concentrated in vacuo and redissolved in CH2Cl2. The solution was filtered through a 0.45 μM PTFE filter and concentrated in vacuo to give the title compound (1.28 g, 92%) as a yellow solid. MS (ESI+) m/z 620.4 (M+H)+.

Workup

  1. customThe resulting reaction mixture
  2. filtrationfiltered through a pad of CELITE®
  3. washrinsing with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionredissolved in CH2Cl2
  6. filtrationThe solution was filtered through a 0.45 μM PTFE
  7. filtrationfilter
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0c83a48a8d614d14b41d76e80d4eebdb
Source dataset
uspto-grants-2014_11
Patent number
US08889712B2

Reaction notes

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