Chlorosuccinimide → 1-[2-(3-chloro-5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]ethanol

HRID 1882016Notes

Reaction equation

HRID 1882016 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[S:27][C:28]([CH:31]([OH:33])[CH3:32])=[CH:29][N:30]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[Cl:34]N1C(=O)CCC1=O>O1CCCC1.C(OCC)(=O)C>[Cl:34][C:23]1[CH:22]=[C:21]([CH:13]([C:10]2[CH:11]=[CH:12][C:7]([S:4]([CH:1]3[CH2:3][CH2:2]3)(=[O:5])=[O:6])=[CH:8][CH:9]=2)[CH2:14][CH:15]2[CH2:16][CH2:17][O:18][CH2:19][CH2:20]2)[NH:25][C:24]=1[C:26]1[S:27][C:28]([CH:31]([OH:33])[CH3:32])=[CH:29][N:30]=1

Participants

5

Reactant 2

HCID 31398ChlorosuccinimideHCID 25107073HCID 25107073, compound

Product 1

HCID 593313541-[2-(3-chloro-5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]ethanol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution (5 mL) of 1-[2-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)-1,3-thiazol-5-yl]ethanol (300 mg) in tetrahydrofuran was added N-chlorosuccinimide (82.3 mg) at 0° C., and the mixture was stirred at 50° C. overnight. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to preparative HPLC to give a mixture of the title compound and a positional isomer thereof (210 mg). The mixture of the obtained positional isomers was dissolved in hexane-2-propanol (700:300, volume ratio, 18.8 mL), and the solution was subjected to HPLC using CHIRALPAK AD (50 mmID×500 mL, manufactured by DAICEL CHEMICAL INDUSTRY LTD.). Using hexane-2-propanol (700:300, volume ratio) as a mobile phase, the solution was eluted at flow rate 60 mL/min and at 30° C., and the both fractions were separated at retention times 41.0 min and 55.0 min, and concentrated. The obtained solid was dissolved in ethyl acetate, and the insoluble material was filtered off. The filtration was concentrated to give the title compound (93.2 mg, yield 29%) as a colorless amorphous solid. MS: 521 (MH+).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with saturated aqueous sodium hydrogen carbonate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto give

Sources & evidence

ORD record
ord-1f4b190f66ba41e3b7b7e9a8dee55d76
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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