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

HRID 924063Notes

Reaction equation

HRID 924063 reaction equation
Br[C:2]1[C:3]([N:23]2[CH2:27][CH2:26][C@H:25]([CH2:28][OH:29])[CH2:24]2)=[N:4][CH:5]=[C:6]([CH:22]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[C:12]([F:21])[CH:11]=1)=[O:8].CC1(C)C(C)(C)OB([C:38]2[CH:39]=[N:40][CH:41]=[C:42]([CH:45]=2)[C:43]#[N:44])O1>>[C:43]([C:42]1[CH:45]=[C:38]([C:2]2[C:3]([N:23]3[CH2:27][CH2:26][C@H:25]([CH2:28][OH:29])[CH2:24]3)=[N:4][CH:5]=[C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:18])([F:19])[F:20])=[C:12]([F:21])[CH:11]=3)=[O:8])[CH:22]=2)[CH:39]=[N:40][CH:41]=1)#[N:44]

Participants

3

Reactant 2

HCID 164142165-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrileHCID 86702609(S)-5-bromo-N-(3-fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide

Product 1

HCID 118195260(S)-5'-Cyano-N-(3-fluoro-4-(trifluoromethoxy)phenyl)-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-(3-fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide (Stage 201.1) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile to afford a white powder. UPLC-MS (Condition 3) tR=1.06 min, m/z=502.4 [M+H]+, m/z=500.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.51-1.66 (m, 1H) 1.79-1.92 (m, 1H) 2.16-2.30 (m, 1H) 2.96 (dd, J=11.00, 6.85 Hz, 1H) 3.10-3.28 (m, 4H) 3.32-3.41 (m, 1H) 4.60 (t, J=5.26 Hz, 1H) 7.50-7.65 (m, 2H) 7.98 (dd, J=13.08, 2.32 Hz, 1H) 8.07 (d, J=2.45 Hz, 1H) 8.40 (t, J=2.20 Hz, 1H) 8.79 (d, J=2.45 Hz, 1H) 8.90 (d, J=1.96 Hz, 1H) 9.02 (d, J=1.96 Hz, 1H) 10.30 (s, 1H).

Workup

  1. customto afford a white powder

Sources & evidence

ORD record
ord-374ddf5539504dd1b1310368d6fbd690
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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