Imidazole → HCID 58573522, compound

HRID 932266Notes

Reaction equation

HRID 932266 reaction equation
[CH2:1]([C@:4]1([CH2:37][CH2:38][OH:39])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:34][CH3:35])[CH2:25][N:26]([CH3:33])[S:27]([CH:30]2[CH2:32][CH2:31]2)(=[O:29])=[O:28])[C:5]1=[O:36])[CH:2]=[CH2:3].N1C=CN=C1.[CH3:45][CH:46]([Si:48](Cl)([CH:52]([CH3:54])[CH3:53])[CH:49]([CH3:51])[CH3:50])[CH3:47]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([C@:4]1([CH2:37][CH2:38][O:39][Si:48]([CH:52]([CH3:54])[CH3:53])([CH:49]([CH3:51])[CH3:50])[CH:46]([CH3:47])[CH3:45])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:34][CH3:35])[CH2:25][N:26]([CH3:33])[S:27]([CH:30]2[CH2:32][CH2:31]2)(=[O:28])=[O:29])[C:5]1=[O:36])[CH:2]=[CH2:3]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 139400Triisopropylsilyl chlorideHCID 58573923HCID 58573923, compound

Product 1

HCID 58573522HCID 58573522, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2.52 g (4.25 mmol) N-((S)-2-((3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-(2-hydroxyethyl)-2-oxopiperidin-1-yl)butyl)-N-methylcyclopropanesulfonamide (Example 408, Step D), DMAP (0.026 g, 0.212 mmol), and imidazole (0.723 g, 10.61 mmol) in DCM (16.98 mL) at 0° C. was added slowly by syringe TIPS-Cl (1.17 mL, 5.52 mmol). The reaction was stirred at ambient temperature, with addition of reagents until reaction was judged complete by LCMS and TLC. The reaction mixture was quenched by addition of 6 mL of MeOH, then extracted with DCM (70 mls×2). The combined organics were washed with water (30 mL), satd. aq. NH4Cl solution (20 mL), dried over Na2SO4, filtered and the filtrate was concentrated. Purification by chromatography on silica gel (eluent: 0 to 40% EtOAc/DCM, gradient elution) provided the title compound as a clear, colorless oil.

Workup

  1. customThe reaction mixture was quenched by addition of 6 mL of MeOH
  2. extractionextracted with DCM (70 mls×2)
  3. washThe combined organics were washed with water (30 mL)
  4. dry with materialaq. NH4Cl solution (20 mL), dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customPurification by chromatography on silica gel (eluent: 0 to 40% EtOAc/DCM, gradient elution)

Sources & evidence

ORD record
ord-a972ce2bd80a4b6592f9c33677f4ff6d
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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