HCID 22350056, compound → HCID 10144746, compound

HRID 896671Notes

Reaction equation

HRID 896671 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[CH3:6][S:7]([C:10]([C:13]1[CH:14]=[C:15]2[C:20](=[C:21]([C:23]3[CH:24]=[C:25]([CH2:29][CH:30]([C:37]4[CH:42]=[CH:41][C:40]([S:43]([CH3:46])(=[O:45])=[O:44])=[CH:39][CH:38]=4)[C:31](N(OC)C)=[O:32])[CH:26]=[CH:27][CH:28]=3)[CH:22]=1)[N:19]=[CH:18][CH:17]=[CH:16]2)([CH3:12])[CH3:11])(=[O:9])=[O:8]>C1COCC1.C(OCC)(=O)C.[Cl-].[NH4+]>[CH:1]1([C:31](=[O:32])[CH:30]([C:37]2[CH:38]=[CH:39][C:40]([S:43]([CH3:46])(=[O:45])=[O:44])=[CH:41][CH:42]=2)[CH2:29][C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([C:21]3[CH:22]=[C:13]([C:10]([S:7]([CH3:6])(=[O:9])=[O:8])([CH3:12])[CH3:11])[CH:14]=[C:15]4[C:20]=3[N:19]=[CH:18][CH:17]=[CH:16]4)[CH:24]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 22350056HCID 22350056, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 10144746HCID 10144746, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

Anhydrous CeCl3 (266 mg, 1.26 mmol) was heated 2 h at 130° C. under high vacuum, refluxed in THF (10 mL) for 1 h then cooled to 0° C. To the resulting white suspension at 0° C. was added freshly prepared cyclopropylmagnesium bromide (0.6M, THF, 2.11 mL, 1.25 mmol) and the resulting mixture stirred at 0° C. for 1 h then cooled to −78° C. The 3-{3-[6-(1-methanesulfonyl-1-methyl-ethyl)-quinolin-8-yl]-phenyl}-2-(4-methanesulfonyl-phenyl)-N-methoxy-N-methyl-propionamide from Step 1 (in THF, 150 mg, 0.25 mmol) was added and the mixture warmed to 0° C. for 1 h, diluted with ethyl acetate and saturated ammonium chloride solution. The organic extracts were washed (H2O), (brine), dried (MgSO4), filtered and concentrated. Purification by flash chromatography (eluting with hexane/ethyl acetate, 1:4) provided the 1-cyclopropyl-3-{3-[6-(1-methanesulfonyl-1-methyl-ethyl)-quinolin-8-yl]-phenyl}-2-(4-methanesulfonyl-phenyl)-propan-1-one compound as a white foam.

Workup

  1. temperaturethen cooled to −78° C
  2. temperaturethe mixture warmed to 0° C. for 1 h
  3. washThe organic extracts were washed (H2O), (brine),
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification
  8. washby flash chromatography (eluting with hexane/ethyl acetate, 1:4)

Sources & evidence

ORD record
ord-fe4d72c71a2e432db3d7b60138b8e720
Source dataset
uspto-grants-2005_07
Patent number
US06919353B2

Reaction notes

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