1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (R)-N-(4-((Chlorodifluoromethyl)thio)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

HRID 73773Notes

Reaction equation

HRID 73773 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].O1CCCCC1[N:34]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][CH:36]=[N:35]1>>[Cl:20][C:17]([F:19])([F:18])[S:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:21]=[C:2]([C:36]3[NH:35][N:34]=[CH:38][CH:37]=3)[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 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86702617(R)-5-bromo-N-(4-((chlorodifluoromethyl)thio)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

Product 1

HCID 72544893(R)-N-(4-((Chlorodifluoromethyl)thio)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 8 using (R)-5-bromo-N-(4-((chlorodifluoromethyl)thio)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide (Stage 18.1) and 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole to afford an off-white solid. HPLC (Condition 4) tR=4.94 min, UPLC-MS (Condition 3) tR=0.99 min, m/z=466.3 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.65-1.88 (m, 2H) 2.86-2.99 (m, 1H) 3.19-3.33 (m, 2H) 3.36-3.51 (m, 1H) 4.13-4.23 (m, 1H) 4.76-4.90 (m, 1H) 6.31-6.42 (m, 1H) 7.65 (d, J=8.21 Hz, 2H) 7.76-7.84 (m, 1H) 7.92 (d, J=8.60 Hz, 2H) 7.98-8.08 (m, 1H) 8.66-8.82 (m, 1H) 10.28 (s, 1H) 12.82-13.14 (m, 1H).

Workup

  1. customto afford an off-white solid

Sources & evidence

ORD record
ord-561f7d166087447d97fc7205b724a9b9
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

Loading…