Ethyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate → 2-(4-Chlorophenyl)-5-({3-[4-(pyrrolidin-1-ylmethyl)phenoxy]azetidin-1-yl}carbonyl)-1,3,4-oxadiazole

HRID 1035166Notes

Reaction equation

HRID 1035166 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:17]=[CH:16][C:9]([CH2:10][N:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)=[CH:8][CH:7]=2)[CH2:2]1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[O:29][C:28]([C:30](OCC)=[O:31])=[N:27][N:26]=2)=[CH:21][CH:20]=1>>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([C:25]2[O:29][C:28]([C:30]([N:1]3[CH2:2][CH:3]([O:5][C:6]4[CH:17]=[CH:16][C:9]([CH2:10][N:11]5[CH2:12][CH2:13][CH2:14][CH2:15]5)=[CH:8][CH:7]=4)[CH2:4]3)=[O:31])=[N:27][N:26]=2)=[CH:23][CH:24]=1

Participants

3

Reactant 2

HCID 46742983Ethyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylateHCID 670165201-(4-(Azetidin-3-yloxy)benzyl)pyrrolidine

Product 1

HCID 565972732-(4-Chlorophenyl)-5-({3-[4-(pyrrolidin-1-ylmethyl)phenoxy]azetidin-1-yl}carbonyl)-1,3,4-oxadiazoleYield 24%

Conditions

Temperature
120 °C

Procedure

A mixture of 1B (1.0 g, 4.3 mmol) and ethyl 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-carboxylate—see e.g. WO97/05131—(1.2 g, 4.7 mmol) was heated at 120° C. for 4 h. The residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent. There was obtained 0.46 g (24%) of 1 as a solid. 1H NMR (500 MHz, CDCl3): δ 1.69-1.88 (m, 4H), 2.38-2.69 (m, 4H), 3.57 (s, 2H), 4.26-4.38 (m, 1H), 4.61-4.68 (m, 1H), 4.72-4.79 (m, 1H), 5.05-5.20 (m, 2H), 6.74 (d, 2H), 7.29 (d, 2H), 7.52 (d, 2H), 8.10 (d, 2H), MS (APCI+) m/z 439 [M+H]+, LC purity: 96%.

Workup

  1. customThe residue was purified by column chromatography on SiO2 using 5% triethylamine in EtOAc as eluent

Sources & evidence

ORD record
ord-aa8ee3f7502b4d449bb10adceb938593
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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