Dimethylformamide → (2S)-methyl 6-(1-(1-benzhydryl-2-methylazetidin-3-yl)-1H-pyrazol-4-yl)-5-(4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1051681Notes

Reaction equation

HRID 1051681 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[C:16]([C:17]3[CH:18]=[N:19][NH:20][CH:21]=3)=[CH:15][CH:14]=[C:13]3[C:8]=2[CH2:9][CH2:10][C@H:11]([CH3:26])[N:12]3[C:22]([O:24][CH3:25])=[O:23])=[CH:4][CH:3]=1.CN(C)C=O.[H-].[Na+].CS(O[CH:41]1[CH2:44][N:43]([CH:45]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:42]1[CH3:58])(=O)=O>O>[CH:45]([N:43]1[CH2:44][CH:41]([N:20]2[CH:21]=[C:17]([C:16]3[C:7]([O:6][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:28][CH:27]=4)=[C:8]4[C:13](=[CH:14][CH:15]=3)[N:12]([C:22]([O:24][CH3:25])=[O:23])[C@@H:11]([CH3:26])[CH2:10][CH2:9]4)[CH:18]=[N:19]2)[CH:42]1[CH3:58])([C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 148524811-Benzhydryl-2-methylazetidin-3-yl methanesulfonateHCID 118076032(S)-methyl 5-(4-fluorophenoxy)-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate

Product 1

HCID 118075635(2S)-methyl 6-(1-(1-benzhydryl-2-methylazetidin-3-yl)-1H-pyrazol-4-yl)-5-(4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylateYield 21%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A 100-mL round-bottom flask was charged with (S)-methyl 5-(4-fluorophenoxy)-2-methyl-6-(1H-pyrazol-4-yl)-3,4-dihydroquinoline-1(2H)-carboxylate (0.300 g, 0.79 mmol) and N,N-dimethylformamide (10 mL), and the solution was cooled to 0° C. Sodium hydride (60% dispersion in mineral oil, 0.047 g, 1.17 mmol) was added, and the resulting mixture stirred for 30 min at room temperature. 1-Benzhydryl-2-methylazetidin-3-yl methanesulfonate (0.286 g, 0.86 mmol) was added, and the resulting mixture stirred overnight at 50° C. The reaction mixture was cooled to room temperature and poured into water (30 mL). The aqueous phase was separated and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 25% ethyl acetate-petroleum ether) to afford (2S)-methyl 6-(1-(1-benzhydryl-2-methylazetidin-3-yl)-1H-pyrazol-4-yl)-5-(4-fluorophenoxy)-2-methyl-3,4-dihydroquinoline-1(2H)-carboxylate (0.100 g, 21%) as yellow oil. MS (ESI, pos. ion) m/z 617 [M+H]+.

Workup

  1. stirringthe resulting mixture stirred overnight at 50° C
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe aqueous phase was separated
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified via column chromatography on silica gel (eluting with 25% ethyl acetate-petroleum ether)

Sources & evidence

ORD record
ord-0d45091bc178488fbb0e0765baef9caa
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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