1,3-Dioxolane-4-methanamine, 2,2-dimethyl- → rac-2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)ethanamine

HRID 2278791Notes

Reaction equation

CS(O[CH2:6][CH2:7][O:8][C:9]1[C:14]([CH3:15])=[CH:13][C:12]([C:16]2[N:20]=[C:19]([C:21]3[CH:26]=[C:25]([O:27][CH3:28])[N:24]=[C:23]([CH:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:22]=3)[O:18][N:17]=2)=[CH:11][C:10]=1[CH2:34][CH3:35])(=O)=O.[CH3:36][C:37]1([CH3:44])[O:41][CH:40]([CH2:42][NH2:43])[CH2:39][O:38]1>C(#N)C>[CH:29]1([C:23]2[CH:22]=[C:21]([C:19]3[O:18][N:17]=[C:16]([C:12]4[CH:13]=[C:14]([CH3:15])[C:9]([O:8][CH2:7][CH2:6][NH:43][CH2:42][CH:40]5[CH2:39][O:38][C:37]([CH3:44])([CH3:36])[O:41]5)=[C:10]([CH2:34][CH3:35])[CH:11]=4)[N:20]=3)[CH:26]=[C:25]([O:27][CH3:28])[N:24]=2)[CH2:30][CH2:31][CH2:32][CH2:33]1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)ethyl methanesulfonate (195 mg, 0.389 mmol) and rac-2,2-dimethyl-1,3-dioxolane-4-methanamine (51 mg, 0.389 mmol) in acetonitrile (6 mL) is stirred at 65° C. for 16 h. The mixture is separated by prep. HPLC to give rac-2-(4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)ethanamine (180 mg) as a white solid. This material is dissolved in 2 N aq. HCl (1 mL) and dioxane (5 mL) and stirred at 60° C. for 1 h. The solvent is evaporated and the crude product is purified by prep. TLC eluting with DCM containing 15% of methanol followed by prep. HPLC to give the title compound (16 mg) as a white solid; LC-MS: tR=0.91 min, [M+H]+=497.11; 1H NMR (CD3OD): δ 7.82 (s, 1H), 7.80 (s, 1H), 7.48 (s, 1H), 7.22 (s, 1H), 4.00 (t, J=5.0 Hz, 2H), 3.98 (s, 3H), 3.82-3.89 (m, 1H), 3.53-3.63 (m, 2H), 3.20-3.30 (m, 1H), 3.08 (t, J=5.0 Hz, 2H), 2.88 (dd, J1=12.1 Hz, J2=3.7 Hz, 1H), 2.70-2.81 (m, 3H), 2.38 (s, 3H), 2.05-2.15 (m, 2H), 1.84-1.95 (m, 4H), 1.69-1.81 (m, 2H), 1.30 (t, J=7.5 Hz, 3H).

Workup

customThe mixture is separated by prep

Sources & evidence

ORD record: ord-653d4386c6c7404ea72ff4704b35c8a8
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133179B2

Reaction notes

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