Ethyl isocyanate → tert-Butyl 3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylamino)carbonylamino]phenyl}piperidyl)-2-oxoethyl]carbamoyl}(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 489701Notes

Reaction equation

HRID 489701 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:44])[C@H:15]([NH:24][C:25]([C@@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:26])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:10][CH2:9]1.[CH2:45]([N:47]=[C:48]=[O:49])C>CC#N>[Cl:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][C@@H:15]([NH:24][C:25]([C@@H:27]2[CH2:36][C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][N:28]2[C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])=[O:26])[C:14]([N:11]2[CH2:12][CH2:13][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[NH:1][C:48]([NH:47][CH3:45])=[O:49])[CH2:9][CH2:10]2)=[O:44])=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 8022Ethyl isocyanateHCID 10189232tert-Butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)-piperidyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}-carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 23587443tert-Butyl 3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylamino)carbonylamino]phenyl}piperidyl)-2-oxoethyl]carbamoyl}(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylateYield 78.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a 50 mL round-bottomed flask equipped with stirring was added tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperidyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Example 20) (462 mg, 0.75 mmol) followed by CH3CN (15 mL) and ethylisocyanate (Chemservice, Inc.) (45.6 mg. 0.80 mmol). The reaction mixture was stirred at RT for 16 h, then the solvent was removed in vacuo. The resulting yellow oil was dissolved in EtOAc (20 mL) and washed with satd NaHCO3 (20 mL) and satd NaCl (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (100% EtOAc) provided the title compound as a white foam (397 mg). MS (ESI, pos. ion) m/z: 674 (M+1); MS (ESI, neg. ion) m/z: 672 (M−1). Calc'd for C37H44ClN5O0: 673.30.

Workup

  1. customTo a 50 mL round-bottomed flask equipped
  2. stirringThe reaction mixture was stirred at RT for 16 h
  3. customthe solvent was removed in vacuo
  4. dissolutionThe resulting yellow oil was dissolved in EtOAc (20 mL)
  5. washwashed with satd NaHCO3 (20 mL) and satd NaCl (20 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-8f20e8fa44404c5c99622a65163ebb8a
Source dataset
uspto-grants-2005_12
Patent number
US06977264B2

Reaction notes

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