Ethyl 5-(4-(difluoromethoxy)phenyl)-1,3,4-oxadiazole-2-carboxylate → (3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-(difluoromethoxy)phenyl)-1,3,4-oxadiazol-2-yl)methanone

HRID 1639511Notes

Reaction equation

HRID 1639511 reaction equation
[F:1][CH:2]([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:14][C:13]([C:15]([O:17]CC)=O)=[N:12][N:11]=2)=[CH:6][CH:5]=1.[NH:21]1[CH2:24][CH:23]([O:25][C:26]2[CH:39]=[CH:38][C:29]([CH2:30][N:31]3[CH2:37][C:33]4([CH2:36][O:35][CH2:34]4)[CH2:32]3)=[CH:28][CH:27]=2)[CH2:22]1>>[CH2:36]1[C:33]2([CH2:32][N:31]([CH2:30][C:29]3[CH:28]=[CH:27][C:26]([O:25][CH:23]4[CH2:22][N:21]([C:15]([C:13]5[O:14][C:10]([C:7]6[CH:6]=[CH:5][C:4]([O:3][CH:2]([F:1])[F:20])=[CH:9][CH:8]=6)=[N:11][N:12]=5)=[O:17])[CH2:24]4)=[CH:39][CH:38]=3)[CH2:37]2)[CH2:34][O:35]1

Participants

3

Reactant 2

HCID 58043152Ethyl 5-(4-(difluoromethoxy)phenyl)-1,3,4-oxadiazole-2-carboxylateHCID 595635036-(4-(Azetidin-3-yloxy)benzyl)-2-oxa-6-azaspiro[3.3]heptane

Product 1

HCID 49801841(3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-(difluoromethoxy)phenyl)-1,3,4-oxadiazol-2-yl)methanoneYield 68.6%

Procedure

Using a similar protocol as described in Example 6 but employing 7A (60 mg, 0.21 mmol) and 3B (50 mg, 0.19 mmol) as starting materials afforded 65 mg (68%) of 7 as a solid. 1H NMR (500 MHz, CDCl3): δ 3.0-4.2 (m, 6H), 4.34 (m, 1H), 4.66 (m, 1H), 4.76 (m, 5H), 5.10 (m, 2H), 6.62 (t, 1H), 6.76 (m, 2H), 7.27 (m, 4H), 8.18 (d, 2H), MS (APCI+) m/z 499 [M+H]+, LC purity: 96%.

Sources & evidence

ORD record
ord-5dc98127805b4843b7c9b7cfbe9a0af5
Source dataset
uspto-grants-2012_02
Patent number
US08110566B2

Reaction notes

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