Pyridine → Tert-butyl 3-(n-{(1r)-1-[(4-chlorophenyl)methyl]-2-[4-(2-{[(2-cyanophenyl)sulfonyl]amino}phenyl)piperidyl]-2-oxoethyl}carbamoyl)(3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 489697Notes

Reaction equation

HRID 489697 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.N1C=CC=CC=1.[C:51]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[S:59](Cl)(=[O:61])=[O:60])#[N:52]>ClCCCl>[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][S:59]([C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=3[C:51]#[N:52])(=[O:61])=[O:60])[CH2:9][CH2:10]2)=[O:44])=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 5223472-Cyanobenzenesulfonyl ChlorideHCID 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 69151038Tert-butyl 3-(n-{(1r)-1-[(4-chlorophenyl)methyl]-2-[4-(2-{[(2-cyanophenyl)sulfonyl]amino}phenyl)piperidyl]-2-oxoethyl}carbamoyl)(3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylateYield 85.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

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) (154 mg, 0.25 mmol), 1,2-dichloroethane (10 mL) and pyridine (0.03 mL, 0.3/5 mmol). The reaction mixture was stirred for 5 min at RT, treated with 2-cyanobenzenesulfonyl chloride (Lancaster Synthesis) (50 mg, 0.25 mmol) and stirred at RT for 16 h. The reaction was quenched with satd NH4Cl (10 mL), the organic layer separated, and the aqueous layer extracted with CH2Cl2 (2×10 mL). The organic fractions were combined, washed with satd NaCl (10 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (100% EtOAc) provided the title compound as a white foam (167 mg). MS (ESI, pos. ion) m/z: 782 (M+1); MS (ESI, neg. ion) m/z: 780 (M−1). Calc'd for C42H44ClN5O6S: 781.27.

Workup

  1. customTo a 50 mL round-bottomed flask equipped
  2. stirringThe reaction mixture was stirred for 5 min at RT
  3. stirringstirred at RT for 16 h
  4. customThe reaction was quenched with satd NH4Cl (10 mL)
  5. customthe organic layer separated
  6. extractionthe aqueous layer extracted with CH2Cl2 (2×10 mL)
  7. washwashed with satd NaCl (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-f298ce8fbcbc4616bc3224281896adec
Source dataset
uspto-grants-2005_12
Patent number
US06977264B2

Reaction notes

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