1,2-Dichloroethane → HCID 69152743, compound

HRID 489684Notes

Reaction equation

HRID 489684 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][N:14]([S:58]([CH3:61])(=[O:60])=[O:59])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH:21]1[CH2:26][CH2:25][N:24]([C:27](=[O:57])[C@H:28]([NH:37][C:38]([C@@H:40]2[CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42][N:41]2[C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])=[O:39])[CH2:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=2)[CH2:23][CH2:22]1.CCO.ClCCCl.NN>CCOC(C)=O>[NH2:3][CH2:12][CH2:13][N:14]([S:58]([CH3:61])(=[O:59])=[O:60])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH:21]1[CH2:26][CH2:25][N:24]([C:27](=[O:57])[C@H:28]([NH:37][C:38]([C@@H:40]2[CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42][N:41]2[C:50]([O:52][C:53]([CH3:56])([CH3:54])[CH3:55])=[O:51])=[O:39])[CH2:29][C:30]2[CH:31]=[CH:32][C:33]([Cl:36])=[CH:34][CH:35]=2)[CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 702EthanolHCID 9321HydrazineHCID 69743730HCID 69743730, compound

Product 1

HCID 69152743HCID 69152743, compoundYield 94.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a 50 mL round-bottomed flask equipped with stirring was added a solution of tert-butyl 3-(N-((1R)-2-[4-(2-{[2-(1,3-dioxoisoindolin-2-yl)ethyl](methylsulfonyl)-amino}phenyl)piperidyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl)carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (Step e) (433.5 mg, 0.5 mmol) in 3:1 EtOH:1,2-dichloroethane (15 mL) followed by hydrazine (Aldrich) (49 mg, 1.5 mmol). The reaction mixture was stirred at 60° C. for 12 h. The organic solvents were removed in vacuo to provide a white solid which 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 (349 mg). MS (ESI, pos. ion) m/z: 738 (M+1); MS (ESI, neg. ion) m/z: 736 (M−1). Calc'd for C38H48ClN5O6S: 737.30.

Workup

  1. customTo a 50 mL round-bottomed flask equipped
  2. stirringThe reaction mixture was stirred at 60° C. for 12 h
  3. customThe organic solvents were removed in vacuo
  4. customto provide a white solid which
  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-9ec0e702bf0346148b8ee30b361e211d
Source dataset
uspto-grants-2005_12
Patent number
US06977264B2

Reaction notes

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