3-Fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine → (R)-N-(4-((Chlorodifluoromethyl)thio)phenyl)-5'-fluoro-2-(3-hydroxypyrrolidin-1-yl)-[3,3'-bipyridine]-5-carboxamide

HRID 924093Notes

Reaction equation

HRID 924093 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]([S:16][C:17]([Cl:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[F:28][C:29]1[CH:30]=[N:31][CH:32]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH:34]=1>>[Cl:20][C:17]([F:19])([F:18])[S:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7]([C:6]2[CH:21]=[C:2]([C:33]3[CH:32]=[N:31][CH:30]=[C:29]([F:28])[CH:34]=3)[C:3]([N:22]3[CH2:26][CH2:25][C@@H:24]([OH:27])[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 86702617(R)-5-bromo-N-(4-((chlorodifluoromethyl)thio)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

Product 1

HCID 118195271(R)-N-(4-((Chlorodifluoromethyl)thio)phenyl)-5'-fluoro-2-(3-hydroxypyrrolidin-1-yl)-[3,3'-bipyridine]-5-carboxamide

Procedure

The title compound was prepared in an analogous fashion to that described infashion to that described in Example 185 using (R)-5-bromo-N-(4-((chlorodifluoromethyl)thio)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide (Stage 217.1) and 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine to afford an off-white foam. HPLC (Condition 4) tR=5.69 min, UPLC-MS (Condition 3) tR=1.09 min, m/z=495.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.77 (m, 1H) 1.79-1.89 (m, 1H) 2.87 (d, J=11.34 Hz, 1H) 3.20 (m, J=11.10, 4.50 Hz, 2H) 3.33-3.44 (m, 1H) 4.19 (br. s, 1H) 4.86 (d, J=3.13 Hz, 1H) 7.66 (d, J=8.60 Hz, 2H) 7.82 (d, J=9.78 Hz, 1H) 7.91 (d, J=8.60 Hz, 2H) 8.06 (d, J=1.00 Hz, 1H) 8.50 (s, 1H) 8.58 (d, J=2.35 Hz, 1H) 8.77 (d, J=1.95 Hz, 1H) 10.27 (s, 1H).

Workup

  1. customto afford an off-white foam

Sources & evidence

ORD record
ord-90bf6e674bc04beea4afb318556cec79
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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