3-(4-Chlorophenyl)-5-(piperidin-4-yl)-1,2,4-oxadiazole → 1-[3-(4-Chloro-3-methyl-phenyl)-1-(3-{4-[3-(4-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-hydroxy-propyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone

HRID 1370996Notes

Reaction equation

HRID 1370996 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH2:13][N:14]([C:17](=[O:19])[CH3:18])[CH2:15][CH2:16][C:11]=3[N:10]([CH2:20][CH:21]3[CH2:23][O:22]3)[N:9]=2)=[CH:4][C:3]=1[CH3:24].[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[N:36]=[C:35]([CH:37]3[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)[O:34][N:33]=2)=[CH:28][CH:27]=1.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Yb+3].CO.C(Cl)Cl>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH2:13][N:14]([C:17](=[O:19])[CH3:18])[CH2:15][CH2:16][C:11]=3[N:10]([CH2:20][CH:21]([OH:22])[CH2:23][N:40]3[CH2:39][CH2:38][CH:37]([C:35]4[O:34][N:33]=[C:32]([C:29]5[CH:30]=[CH:31][C:26]([Cl:25])=[CH:27][CH:28]=5)[N:36]=4)[CH2:42][CH2:41]3)[N:9]=2)=[CH:4][C:3]=1[CH3:24]

Participants

6

Reactant 4

HCID 7159093-(4-Chlorophenyl)-5-(piperidin-4-yl)-1,2,4-oxadiazoleHCID 2733225Ytterbium triflateHCID 21226129Dichloromethane methanolHCID 222936051-[3-(4-Chloro-3-methyl-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone

Product 1

HCID 101216531-[3-(4-Chloro-3-methyl-phenyl)-1-(3-{4-[3-(4-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-2-hydroxy-propyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanoneYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-[3-(4-Chloro-3-methyl-phenyl)-1-oxiranylmethyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (0.069 g. 0.20 mmol) was dissolved in CH2Cl2 (1 mL), and 4-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]piperidine (0.105 g, 0.4 mmol) was added, followed by Yb(OTf)3 (0.031 g, 0.22 mmol). The mixture was stirred at room temperature for 16 h. Preparative TLC (silica, 7.5% MeOH/CH2Cl2) afforded 84 mg (69%) of the title compound. MS (electrospray): exact mass calculated for C31H34Cl2N6O3, 608.21; m/z found, 609.2 [M++H]. 1H NMR (400 MHz, CDCl3, 1:1 mixture of rotamers): 8.00 (d, J=8.4 Hz, 2H), 7.56-7.53 (m, 1H), 7.48-7.42 (d, J=8.6 Hz, 2H), 7.41-7.30 (m, 2H), 4.84 and 4.73 (A and B of AB quartet J=15.6 Hz, 1H), 4.62 (br s, 1H), 4.25-4.13 (m, 2H), 4.10-3.98 (m, 2H), 3.90-3.70 (m, 2H), 3.04-2.71 (m, 5H), 2.51-2.40 (m, 6H), 2.30-2.15 (m, 6H), 2.10-1.90 (m, 2H).

Sources & evidence

ORD record
ord-d264500072d64638b4a8b8df0cad58d7
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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