1,2-Dichloroethane → HCID 131725242, compound

HRID 489686Notes

Reaction equation

HRID 489686 reaction equation
CO[CH:3](OC)[CH2:4][N:5]([CH3:28])[C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23]C(C)(C)C)=O)[CH2:17][CH2:16]1)=[O:7].C(O)(C(F)(F)F)=O.[NH:38]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[C@@H:39](C(O)=O)[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl>[Cl:47][C:44]1[CH:43]=[CH:42][C:41]([CH2:40][C@@H:39]([NH:38][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[C:21]([N:18]2[CH2:17][CH2:16][CH:15]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[N:8]3[CH:3]=[CH:4][N:5]([CH3:28])[C:6]3=[O:7])[CH2:20][CH2:19]2)=[O:23])=[CH:46][CH:45]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 7018791N-Boc-4-chloro-D-phenylalanineHCID 69143047HCID 69143047, compound

Product 1

HCID 131725242HCID 131725242, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 150 mL round-bottomed flask equipped with stirring was added tert-butyl 4-(2-{[(2,2-dimethoxyethyl)methylamino]carbonylamino}phenyl)-piperidinecarboxylate (Step a) (1.4 g, 3.3 mmol) and a 50% aqueous TFA soln (50 mL). The reaction mixture was stirred at RT for 2 h, then concentrated in vacuo. The residue was dissolved in CH2Cl2 (10 mL), stirred at 0° C. and treated with Boc-p-Cl-D-PheOH (Advanced ChemTech) (0.94 g, 3.15 mmol), HOBT (Novabiochem) (0.425 g, 3.15 mmol), TEA (Aldrich) (0.44 mL, 3.15 mmol) and EDC (Advanced ChemTech) (0.91 g, 4.7 mmol). The reaction was warmed to RT over 2 h and stirred at RT for 12 h. The reaction mixture was diluted with CH2Cl2 (60 mL) and the organic phase was washed with satd NaHCO3 (50 mL), and satd NaCl (50 mL), dried over Na2SO4, and concentrated in vacuo. Purification by silica gel chromatography (100% EtOAc) provided the title compound as a pale yellow oil (0.55 g). MS (ESI, pos. ion) m/z: 539 (M+1). Calc'd for C29H35ClN4O4: 538.23.

Workup

  1. customTo a 150 mL round-bottomed flask equipped
  2. stirringThe reaction mixture was stirred at RT for 2 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in CH2Cl2 (10 mL)
  5. stirringstirred at 0° C.
  6. stirringstirred at RT for 12 h
  7. washthe organic phase was washed with satd NaHCO3 (50 mL), and satd NaCl (50 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customPurification by silica gel chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-76c05bff9eda4bb6af5265f70bf9e916
Source dataset
uspto-grants-2005_12
Patent number
US06977264B2

Reaction notes

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