Hydrochloric Acid → 2-Azetidin-1-yl-5-(3'-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-pyridine

HRID 1632074Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][CH:11]=[C:10]([CH2:16][C:17]3[CH:18]=[CH:19][C:20](F)=[N:21][CH:22]=3)[C:9]=2[F:24])[CH:5]=[CH:6][CH:7]=1.[NH:25]1[CH2:28][CH2:27][CH2:26]1.N12CCCN=C1CCCCC2.Cl>O>[N:25]1([C:20]2[CH:19]=[CH:18][C:17]([CH2:16][C:10]3[C:9]([F:24])=[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)[C:13]([O:14][CH3:15])=[CH:12][CH:11]=3)=[CH:22][N:21]=2)[CH2:28][CH2:27][CH2:26]1

Participants

Conditions

Temperature: 160 °C

Procedure

In an 8 mL vial equipped with a stir bar was placed 5-(3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-2-fluoro-pyridine (P-456,150 mg, 0.434 mmol), azetidine (88.0 uL, 1.30 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (306 uL, 2.17 mmol). The mixture was heated to 160° C. for 1 hour and then cooled to room temperature. The reaction mixture was treated with water (4 mL) and 1M HCl (6 mL). The aqueous portion was extracted with dichloromethane (2×30 mL), the organic portions were combined, washed with brine (15 mL), dried (MgSO4) and concentrated to produce 156 mg of P-569 as a white solid in 94% yield.

Workup

customIn an 8 mL vial equipped with a stir bar
temperaturecooled to room temperature
extractionThe aqueous portion was extracted with dichloromethane (2×30 mL)
washwashed with brine (15 mL)
dry with materialdried (MgSO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-b78b5b0b8c4c4f59bdd6d7bdeaff3d5b
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791267B2

Reaction notes

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