3-Fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine → (S)-N-(4-(Chlorodifluoromethoxy)phenyl)-5'-fluoro-2-(3-(hydroxymethyl)pyrrolidin-1-yl)-[3,3'-bipyridine]-5-carboxamide

HRID 924025Notes

Reaction equation

HRID 924025 reaction equation
Br[C:2]1[C:3]([N:22]2[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[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:29][C:30]1[CH:31]=[N:32][CH:33]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:35]=1>>[Cl:20][C:17]([F:19])([F:18])[O:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7]([C:6]2[CH:21]=[C:2]([C:34]3[CH:33]=[N:32][CH:31]=[C:30]([F:29])[CH:35]=3)[C:3]([N:22]3[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]3)=[N:4][CH:5]=2)=[O:8])=[CH:11][CH:12]=1

Participants

3

Reactant 2

HCID 164142683-Fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86702603(S)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide

Product 1

HCID 118195247(S)-N-(4-(Chlorodifluoromethoxy)phenyl)-5'-fluoro-2-(3-(hydroxymethyl)pyrrolidin-1-yl)-[3,3'-bipyridine]-5-carboxamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 169 using (S)-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide (Stage 174.1) and 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine to afford an off-white solid. HPLC (Condition 4) tR=5.29 min, UPLC-MS (Condition 3) tR=1.06 min, m/z=493.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.47-1.63 (m, 1H) 1.83 (m, J=5.90 Hz, 1H) 2.14-2.28 (m, 1H) 2.96 (dd, J=10.95, 7.04 Hz, 1H) 3.10-3.38 (m, 5H) 4.60 (t, J=5.08 Hz, 1H) 7.32 (d, J=8.21 Hz, 2H) 7.77-7.88 (m, 3H) 8.05 (d, J=1.00 Hz, 1H) 8.50 (s, 1H) 8.57 (d, J=1.96 Hz, 1H) 8.76 (d, J=1.00 Hz, 1H) 10.16 (s, 1H).

Workup

  1. customto afford an off-white solid

Sources & evidence

ORD record
ord-15d0ab33bca84972b72aee3eec3decf5
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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