5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile → (S)-N-(4-(Chlorodifluoromethoxy)phenyl)-5'-cyano-2-(3-(hydroxymethyl)pyrrolidin-1-yl)-[3,3'-bipyridine]-5-carboxamide

HRID 924026Notes

Reaction equation

HRID 924026 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].CC1(C)C(C)(C)OB([C:37]2[CH:38]=[N:39][CH:40]=[C:41]([CH:44]=2)[C:42]#[N:43])O1>>[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:37]3[CH:38]=[N:39][CH:40]=[C:41]([C:42]#[N:43])[CH:44]=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 164142165-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrileHCID 86702603(S)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide

Product 1

HCID 118195330(S)-N-(4-(Chlorodifluoromethoxy)phenyl)-5'-cyano-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 151 using (S)-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide (Stage 174.1) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile to afford a yellow solid. UPLC-MS (Condition 3) tR=1.05 min, m/z=498.5 [M+H]+, m/z=500.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.66 (m, 1H) 1.78-1.92 (m, 1H) 2.17-2.30 (m, 1H) 2.96 (dd, J=11.00, 6.85 Hz, 1H) 3.11-3.28 (m, 4H) 3.32-3.42 (m, 1H) 4.60 (t, J=5.26 Hz, 1H) 7.34 (d, J=9.05 Hz, 2H) 7.81-7.91 (m, 2H) 8.08 (d, J=2.20 Hz, 1H) 8.40 (t, J=2.08 Hz, 1H) 8.79 (d, J=2.45 Hz, 1H) 8.91 (d, J=2.20 Hz, 1H) 9.01 (d, J=1.96 Hz, 1H) 10.16 (s, 1H).

Workup

  1. customto afford a yellow solid

Sources & evidence

ORD record
ord-d7965752a3064445be5544a4b1a07836
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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