Chloride → HCID 68951848, compound

HRID 1518090Notes

Reaction equation

HRID 1518090 reaction equation
[Cl-:1].[CH2:2]([O:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH:15]([C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:23]2[C:32]([CH2:33]O)=[CH:31][C:30]3[C:25](=[CH:26][C:27]([F:36])=[C:28]([F:35])[CH:29]=3)[N:24]=2)[CH2:14][CH2:13]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:2]([O:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH:15]([C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:23]2[C:32]([CH2:33][Cl:1])=[CH:31][C:30]3[C:25](=[CH:26][C:27]([F:36])=[C:28]([F:35])[CH:29]=3)[N:24]=2)[CH2:14][CH2:13]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 312ChlorideHCID 962WaterHCID 81531DiisopropylethylamineHCID 57861260HCID 57861260, compound

Product 1

HCID 68951848HCID 68951848, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methaneslufonyl chloride (5.5 mL, 71 mmol) is added dropwise to a mixture of [2-((R)-2-{4-[2-(benzyloxy)ethyl]cyclohexyl}pyrrolidin-1-yl)-6,7-difluoroquinolin-3-yl]methanol (13.7 g, 28.5 mmol) and N,N-diisopropylethylamine (DIPEA, 12.4 mL, 71 mmol) in toluene (150 mL) at 5° C., and the reaction mixture is stirred at ambient temperature for 2 hours. To the mixture, water and ethyl acetate are added and the organic layer is washed with sat. NaHCO3 aq, brine, dried over magnesium sulfate, filtered and concentrated in vacuo to give crude 2-((R)-2-{4-[2-(benzyloxy)ethyl]cyclohexyl}pyrrolidin-1-yl)-3-(chloromethyl)-6,7-difluoroquinoline. To a mixture of 2-((R)-2-{4-[2-(benzyloxy)ethyl]cyclohexyl}pyrrolidin-1-yl)-3-(chloromethyl)-6,7-difluoroquinoline and N-[3,5-bis(trifluoromethyl)benzyl]-N-(2-methyl-2H-tetrazol-5-yl)amine (13.9 g, 43 mmol) in DMF (120 mL) is added potassium tert-butoxide (4.80 g, 43 mmol) at 5° C. The resulting mixture is stirred for 1 hour at the same temperature. After adding sat. NH4Cl aq., the mixture is extracted with ethyl acetate. The combined organic layer is washed with water, brine, dried over magnesium sulfate, filtrated, and concentrated. The resulting mixture is purified by silica gel column chromatography to give trans-N-[2-((R)-2-{4-[2-(benzyloxy)ethyl]cyclohexyl}pyrrolidin-1-yl)-6,7-difluoroquinolin-3-ylmethyl]-N-[3,5-bis(trifluoromethyl)benzyl](2-methyl-2H-tetrazol-5-yl)amine as a yellow amorphous.

Workup

  1. washthe organic layer is washed with sat. NaHCO3 aq, brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7200ec69bd8c4db3a1381f0ea6edc802
Source dataset
uspto-grants-2012_07
Patent number
US08232403B2

Reaction notes

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