1,2-Dichloroethane → HCID 178502343, compound

HRID 1429259Notes

Reaction equation

HRID 1429259 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C@@H:15]([C:16]3[C:17]([F:30])=[CH:18][C:19]4[N:23]=[C:22]([C@@H:24]5[CH2:28][CH2:27][CH2:26][NH:25]5)[NH:21][C:20]=4[CH:29]=3)[CH2:14][CH2:13][C@@H:12]2[C:31]2[C:32]([F:45])=[CH:33][C:34]3[N:38]=[C:37]([C@@H:39]4[CH2:43][CH2:42][CH2:41][NH:40]4)[NH:36][C:35]=3[CH:44]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C[N:47]1[CH2:52][CH2:51][O:50]CC1.[CH3:53][O:54][C:55]([NH:57][C@@H:58]([CH:62]([CH3:64])[CH3:63])[C:59](O)=[O:60])=[O:56].C(Cl)CCl.[CH:69]1[CH:70]=CC2N(O)N=NC=2[CH:74]=1.C[CH2:80][O:81][C:82](C)=[O:83]>CN(C=O)C>[CH3:80][O:81][C:82](=[O:83])[NH:47][C@@H:52]([CH:69]([CH3:70])[CH3:74])[C:51]([N:25]1[CH2:26][CH2:27][CH2:28][C@H:24]1[C:22]1[NH:23][C:19]2[CH:18]=[C:17]([F:30])[C:16]([C@H:15]3[CH2:14][CH2:13][C@H:12]([C:31]4[C:32]([F:45])=[CH:33][C:34]5[N:38]=[C:37]([C@@H:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:59](=[O:60])[C@@H:58]([NH:57][C:55]([O:54][CH3:53])=[O:56])[CH:62]([CH3:64])[CH3:63])[NH:36][C:35]=5[CH:44]=4)[N:11]3[C:8]3[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:10][CH:9]=3)=[CH:29][C:20]=2[N:21]=1)=[O:50]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 8857Ethyl AcetateHCID 757711-HydroxybenzotriazoleHCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 58226557HCID 58226557, compound

Product 1

HCID 178502343HCID 178502343, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 6,6′-[(2R,5R)-1-(4-tert-butylphenyl)pyrrolidine-2,5-diyl]bis{5-fluoro-2-[(2S)-pyrrolidin-2-yl]-1H-benzimidazole} was added DMF (1.0 mL) followed by N-methylmorpholine (0.045 mL, 0.41 mmol), (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid (15 mg, 0.09 mmol), EDC (20 mg, 0.1 mmol) and HOBT (16 mg, 0.1 mmol). The solution was stirred at room temperature for 18 hours. The reaction mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The product was purified by reverse-phase HPLC chromatography (5-100% CH3CN/0.1% TFA-H2O); the desired fractions were neutralized with aqueous NaHCO3 solution, extracted with EtOAc, dried, filtered and solvent evaporated to give the title compound (6.7 mg, 7.2 μmol, 18%): 1H NMR (400 MHz, CDCl3) δ ppm 10.48 (m, 1H) 10.25 (m, 1H) 7.39 (m, 1H) 7.14 (m, 1H) 6.98 (m, 3H) 6.29 (m, 1H) 5.54 (br s, 1H) 5.34 (br s, 4H) 4.31 (m, 1H) 3.82 (m, 2H) 3.70 (s, 6H) 3.51-3.65 (m, 2H) 3.03 (br s, 2H) 2.51 (br s, 2H) 2.23-2.40 (m, 2H) 2.14 (m, 4H) 1.95 (m, 4H) 1.27 (m, 2H) 1.09-1.23 (m, 9H) 1.07 (m, 3H) 0.87 (m, 9H) 0.67-0.79 (m, 2H); MS (ESI) m/z 924 (M+H)+.

Workup

  1. washwashed with H2O and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe product was purified by reverse-phase HPLC chromatography (5-100% CH3CN/0.1% TFA-H2O)
  6. extractionextracted with EtOAc
  7. customdried
  8. filtrationfiltered
  9. customsolvent evaporated

Sources & evidence

ORD record
ord-5682e835587e4179869b72daa2d038fb
Source dataset
uspto-grants-2015_01
Patent number
US08937150B2

Reaction notes

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