4-(Pyrrolidin-2-yl)pyridine → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-9-(2-(pyridin-4-yl)pyrrolidin-1-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine

HRID 1530520Notes

Reaction equation

Cl[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][N:15]=1)[C:12]1[N:8]([CH:9]=[C:10]([C:16]3[N:20]([CH:21]([CH3:23])[CH3:22])[N:19]=[CH:18][N:17]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2.[NH:24]1[CH2:28][CH2:27][CH2:26][CH:25]1[C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1>CN1C(=O)CCC1>[CH:21]([N:20]1[C:16]([C:10]2[N:11]=[C:12]3[C:13]4[CH:14]=[N:15][C:2]([N:24]5[CH2:28][CH2:27][CH2:26][CH:25]5[C:29]5[CH:30]=[CH:31][N:32]=[CH:33][CH:34]=5)=[CH:3][C:4]=4[O:5][CH2:6][CH2:7][N:8]3[CH:9]=2)=[N:17][CH:18]=[N:19]1)([CH3:23])[CH3:22]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 12-chloro-4-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (150 mg, 0.450 mmol), TEA (0.5 mL), and 4-(pyrrolidin-2-yl)pyridine (134 mg, 0.900 mmol) in NMP (0.5 mL) was stirred at 150° C. for 24 h under nitrogen atmosphere. The resulting mixture was purified by reverse phase combiflash eluting with a 0-50% gradient of CH3CN in 0.3% NH4HCO3 to give 136, which was further purified by chiral HPLC (AD column, 30% EtOH (0.1% DEA) in n-Hexane isocratic) to separate the (R) and (S) enantiomers, 23 mg of one enantiomer and 28 mg of the other (26% total yield).

Workup

customThe resulting mixture was purified by reverse phase combiflash
washeluting with a 0-50% gradient of CH3CN in 0.3% NH4HCO3

Sources & evidence

ORD record: ord-3ed7bc97df154b6cb67993d050eb371e
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090628B2

Reaction notes

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