1,2-Dichloroethane → HCID 69740438, compound

HRID 489662Notes

Reaction equation

HRID 489662 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C@@H:10]([NH:30][C:31](OC(C)(C)C)=[O:32])[C:11]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[NH:25][S:26]([CH3:29])(=[O:28])=[O:27])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[N:39]1([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH2:41][C@H:40]1C(O)=O.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CCOC(C)=O.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C@@H:10]([NH:30][C:31]([C@@H:40]2[CH2:41][C:42]3[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:48][N:39]2[C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])=[O:32])[C:11]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[NH:25][S:26]([CH3:29])(=[O:27])=[O:28])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 181649HOAtHCID 664088(3S)-2-((tert-butoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 23587430HCID 23587430, compound

Product 1

HCID 69740438HCID 69740438, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a round-bottomed flask equipped with stirring was added N-[(1R)-1-[(3,4-dichlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}-piperidyl)-2-oxoethyl]-(tert-butoxy)carboxamide (Step a) (0.455 g, 0.8 mmol) and a saturated soln of anhydrous HCl in EtOAc (20 mL). The reaction mixture was stirred at RT for 1 h then concentrated in vacuo to provide a solid. The solid was dissolved in DMF (10 mL), stirred at 0° C. and treated with Boc-L-TicOH (Advanced ChemTech) (0.25 g, 0.9 mmol), HOAT (Aldrich) (0.122 g, 0.9 mmol), TEA (Aldrich) (0.188 mL, 1.35 mmol) then EDC (Advanced ChemTech) (0.26 g, 1.35 mmol). The reaction mixture was warmed to RT over 2 h, then stirred at RT for 12 h. The reaction mixture was diluted with EtOAc (70 mL), washed with satd NaHCO3, (50 mL), satd NaCl (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography (1:1 EtOAc:hexane then 100% EtOAc) provided the title compound as a white foam (0.54 g). MS (ESI, pos. ion) m/z: 729 (M+1); MS (ESI, neg. ion) m/z: 727 (M−1). Calc'd for C36H42Cl2N4O6S: 728.22.

Workup

  1. customTo a round-bottomed flask equipped
  2. stirringThe reaction mixture was stirred at RT for 1 h
  3. concentrationthen concentrated in vacuo
  4. customto provide a solid
  5. stirringstirred at 0° C.
  6. stirringstirred at RT for 12 h
  7. washwashed with satd NaHCO3, (50 mL), satd NaCl (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel chromatography (1:1 EtOAc

Sources & evidence

ORD record
ord-5219560d5b864069985600e271718659
Source dataset
uspto-grants-2005_12
Patent number
US06977264B2

Reaction notes

Loading…