3-Nitrophenylboronic Acid → 1-[5-(3'-Chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-pyridin-2-yl]-pyrrolidin-3-ol

HRID 1632067Notes

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.[N+](C1C=C(B(O)O)C=CC=1)([O-])=[O:26].N12[CH2:47][CH2:46][CH2:45][N:44]=[C:43]1CCCCC2>ClCCl>[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]([N:44]4[CH2:43][CH2:47][CH:46]([OH:26])[CH2:45]4)=[N:21][CH:22]=3)[C:9]=2[F:24])[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To 5-(3′-chloro-2-fluoro-6-methoxy-biphenyl-3-ylmethyl)-2-fluoro-pyridine (P-456, 0.3 g, 0.87 mmol) and 3-pyrrolidinol (2) (0.15 g, 1.74 mmol) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (0.66 g, 4.34 mmol). The reaction mixture was stirred and heated at 100° C. for 2.5 h, cooled to room temperature, diluted with dichloromethane (8 mL), washed with 0.5 N HCl (2×4 mL), dried with Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography using 5% methanol in dichloromethane to afford 0.27 g (75%) of P-601 as white solid. 1H NMR (DMSO-d6, 400 MHz): 7.95 (s, 1H), 7.2-7.46 (m, 6H), 6.91 (d, J=8.4 Hz, 1H), 6.35 (d, J=8.4 Hz, 1H), 4.9 (d, J=3.6 Hz, 1H), 4.32-4.4 (m, 1H), 3.76 (s, 2H), 3.71 (s, 3H), 3.12-3.45 (m, 4H), 1.8-2.05 (m, 2H) ppm; MS (APCI+): 413.1 (M+1), LC-MS: 91.6%.

Workup

temperaturecooled to room temperature
washwashed with 0.5 N HCl (2×4 mL)
dry with materialdried with Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel column chromatography
customto afford 0.27 g (75%) of P-601 as white solid

Sources & evidence

ORD record: ord-05784495b850448fa27dea73baba6d25
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791267B2

Reaction notes

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