5-Fluoro-2-methylphenylboronic acid → (R)-N-(4-(Chlorodifluoromethoxy)phenyl)-5-(5-fluoro-2-methylphenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

HRID 924155Notes

Reaction equation

HRID 924155 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([Cl:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[F:28][C:29]1[CH:30]=[CH:31][C:32]([CH3:38])=[C:33](B(O)O)[CH:34]=1>>[Cl:20][C:17]([F:19])([F:18])[O:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:21]=[C:2]([C:31]3[CH:30]=[C:29]([F:28])[CH:34]=[CH:33][C:32]=3[CH3:38])[C:3]([N:22]3[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]3)=[N:4][CH:5]=2)=[CH:11][CH:12]=1

Participants

3

Reactant 2

HCID 27831905-Fluoro-2-methylphenylboronic acidHCID 72545856(R)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

Product 1

HCID 89908374(R)-N-(4-(Chlorodifluoromethoxy)phenyl)-5-(5-fluoro-2-methylphenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 290 using (R)-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide (Stage 171.1) and 5-Fluoro-2-methylphenylboronic acid to afford a white solid. HPLC (Condition 10) tR=6.424 min, UPLC-MS (Condition 11) m/z=492.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.60-1.92 (m, 2H) 1.94-2.11 (m, 3H) 2.78-3.03 (m, 1H) 3.07-3.28 (m, 3H) 4.11-4.23 (m, 1H) 4.76-4.94 (m, 1H) 7.10-7.19 (m, 1H) 7.23-7.31 (m, 1H) 7.33 (d, J=8.99 Hz, 3H) 7.86 (d, J=8.99 Hz, 2H) 7.91 (m, J=2.30 Hz, 1H) 8.73-8.79 (m, 1H) 10.08-10.17 (m, 1H).

Workup

  1. customto afford a white solid

Sources & evidence

ORD record
ord-4b78b5d1dfa345b1aa2c31e094591f25
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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