1-Cyclopropylpiperidin-4-ol → HCID 66919107, compound

HRID 2354192Notes

Reaction equation

HRID 2354192 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:26])=[C:11]([NH:13][C:14](=[O:25])[C:15]3[CH:20]=[C:19](F)[CH:18]=[CH:17][C:16]=3[N+:22]([O-:24])=[O:23])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1.[CH:27]1([N:30]2[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32][CH2:31]2)[CH2:29][CH2:28]1>>[CH:1]1([NH:4][C:5]([C:7]2[CH:8]=[CH:9][C:10]([CH3:26])=[C:11]([NH:13][C:14](=[O:25])[C:15]3[CH:20]=[C:19]([O:36][CH:33]4[CH2:34][CH2:35][N:30]([CH:27]5[CH2:29][CH2:28]5)[CH2:31][CH2:32]4)[CH:18]=[CH:17][C:16]=3[N+:22]([O-:24])=[O:23])[CH:12]=2)=[O:6])[CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 515828091-Cyclopropylpiperidin-4-olHCID 669189745-fluoro-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-nitrobenzamide

Product 1

HCID 66919107HCID 66919107, compound

Procedure

N-benzyl-N-methyl-4-oxopiperidiumbromide (3.68 g) in water (6 ml) was added portionwise over 30 minutes to a stirred mixture of N-cyclopropylamine (0.404 g) and potassium carbonate in ethanol (15 ml) at 75° C. The mixture was stirred at 75° C. for 45 minutes. The reaction mixture was evaporated, took up into water (20 ml) and extracted into methylene chloride. The organic extracts were combined and concentrated under reduced pressure and the residue was triturated with ether and the soluble fraction was isolated by evaporation (1.11 g) to give N-cyclopropyl-4-piperidone; NMR Spectrum: (CDCl3) 0.50 (m, 4H), 1.73 (m, 1H), 2.40 (t, 4H), 2.91 (t, 4H). B) Sodium borohydride (0.085 g) was added to a stirred solution of N-cyclopropyl-4-piperidone (0.312 g) in ethanol under an atmosphere of argon. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was evaporated, took up into water (20 ml) and extracted into methylene chloride. The organic extracts were combined and concentrated under reduced pressure to give N-cyclopropyl-4-piperidinol (0.298 g); NMR Spectrum: (CDCl3) 0.50 (m, 4H), 1.35 (s, 1H), 1.55 (m, 2H), 1.86 (m, 2H) 2.34 (m, 2H), 2.89 (m, 2H), 3.70 (m, 1H). C) Using an analogous procedure to that described paragraph (A) in the portion of Example 15 which is concerned with the preparation of starting material, N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-fluoro-2-nitrobenzamide was reacted with N-cyclopropyl-4-piperidol to give N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-[(1-cyclopropylpiperidine-4-yl)oxy]-2-nitrobenzamide; Mass Spectrum: M+H+ 479.

Sources & evidence

ORD record
ord-03fe7579fd364d6e86694682f1ed03a4
Source dataset
uspto-grants-2010_07
Patent number
US07750154B2

Reaction notes

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