Ammonium Chloride → HCID 178482000, compound

HRID 1960047Notes

Reaction equation

HRID 1960047 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][CH:11]1[CH2:16][CH2:15][CH:14]([C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2[C:22]2[C:31]([CH2:32]Cl)=[CH:30][C:29]3[C:24](=[CH:25][C:26]([F:35])=[C:27]([F:34])[CH:28]=3)[N:23]=2)[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:36][C:37]([F:57])([F:56])[C:38]1[CH:39]=[C:40]([CH:49]=[C:50]([C:52]([F:55])([F:54])[F:53])[CH:51]=1)[CH2:41][NH:42][C:43]1[N:44]=[N:45][N:46]([CH3:48])[N:47]=1.CC(C)([O-])C.[K+].[NH4+].[Cl-]>CN(C=O)C>[CH2:1]([O:8][CH2:9][CH2:10][C@H:11]1[CH2:16][CH2:15][C@H:14]([C@H:17]2[CH2:21][CH2:20][CH2:19][N:18]2[C:22]2[C:31]([CH2:32][N:42]([C:43]3[N:44]=[N:45][N:46]([CH3:48])[N:47]=3)[CH2:41][C:40]3[CH:39]=[C:38]([C:37]([F:36])([F:56])[F:57])[CH:51]=[C:50]([C:52]([F:53])([F:54])[F:55])[CH:49]=3)=[CH:30][C:29]3[C:24](=[CH:25][C:26]([F:35])=[C:27]([F:34])[CH:28]=3)[N:23]=2)[CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 230732215-[N-(3',5'-Bistrifluoromethylbenzyl)amino]-2-methyltetrazoleHCID 23665647Potassium tert-butoxideHCID 68951848HCID 68951848, compound

Product 1

HCID 178482000HCID 178482000, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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. extractionthe mixture is extracted with ethyl acetate
  2. washThe combined organic layer is washed with water, brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltrated
  5. concentrationconcentrated
  6. customThe resulting mixture is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-90ee4b02b3ab4251a2d4c4e56193ab73
Source dataset
uspto-grants-2013_04
Patent number
US08410275B2

Reaction notes

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