5-(Oxiran-2-yl)-2-(1H-tetrazol-1-yl)pyridine → 5-[(1R)-1-hydroxy-2-[4-[2-hydroxy-2-[6-(tetrazol-1-yl)-3-pyridyl]ethyl]piperazin-1-yl]ethyl]-4-methyl-3H-isobenzofuran-1-one

HRID 2281352Notes

Reaction equation

[O:1]1[CH2:3][CH:2]1[C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[N:13][N:12]=[N:11]2)=[N:8][CH:9]=1.Cl.[C@@H:16]12[N:23]([CH2:24][C@@H:25]([C:27]3[C:28]([CH3:37])=[C:29]4[C:33](=[CH:34][CH:35]=3)[C:32](=[O:36])[O:31][CH2:30]4)[OH:26])[C@@H:20](CC1)[CH2:19][NH:18][CH2:17]2>C(O)C>[OH:26][C@H:25]([C:27]1[C:28]([CH3:37])=[C:29]2[C:33](=[CH:34][CH:35]=1)[C:32](=[O:36])[O:31][CH2:30]2)[CH2:24][N:23]1[CH2:16][CH2:17][N:18]([CH2:3][CH:2]([OH:1])[C:4]2[CH:9]=[N:8][C:7]([N:10]3[CH:14]=[N:13][N:12]=[N:11]3)=[CH:6][CH:5]=2)[CH2:19][CH2:20]1

Participants

Conditions

Temperature: 150 °C

Procedure

To a microwave tube were added 5-(oxiran-2-yl)-2-(1H-tetrazol-1-yl)pyridine (INTERMEDIATE 32) (100 mg, 0.53 mmol), (R)-5-(1-hydroxy-2-(piperazin-1-yl)ethyl)-4-methylisobenzofuran-1(3H)-one (INTERMEDIATE 12) (175 mg, 0.63 mmol), and ethanol (3.0 mL). The mixture was heated in the microwave for 1 hour at 150° C. The solvent was evaporated and the crude product was purified by Mass Directed Reverse-Phase HPLC Chromatography to give 5-[(1R)-1-hydroxy-2-[4-[2-hydroxy-2-[6-(tetrazol-1-yl)-3-pyridyl]ethyl]piperazin-1-yl]ethyl]-4-methyl-3H-isobenzofuran-1-one.

Workup

customThe solvent was evaporated
customthe crude product was purified by Mass Directed Reverse-Phase HPLC Chromatography

Sources & evidence

ORD record: ord-ec3742b12619480fadcde5f5e2863b27
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139585B2

Reaction notes

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