1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (S)-6-(3-(Hydroxymethyl)pyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide

HRID 73757Notes

Reaction equation

HRID 73757 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]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].O1CCCCC1[N:35]1[C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][CH:37]=[N:36]1>>[OH:28][CH2:27][C@H:24]1[CH2:25][CH2:26][N:22]([C:3]2[C:2]([C:37]3[NH:36][N:35]=[CH:39][CH:38]=3)=[CH:21][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:23]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 86702606(S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide

Product 1

HCID 72544676(S)-6-(3-(Hydroxymethyl)pyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 10 using (S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide (Stage 12.1) and 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole to afford a pale yellow powder. UPLC-MS (Condition 3) tR=0.99 min, m/z=464.2 [M+H]+, m/z=462.2 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) d ppm 1.48-1.64 (m, 1H) 1.76-1.93 (m, 1H) 2.15-2.27 (m, 1H) 3.04 (dd, J=11.49, 7.09 Hz, 1H) 3.18-3.26 (m, 2H) 3.27-3.29 (m, 1H) 3.32-3.41 (m, 2H) 4.60 (br. s, 1H) 6.39 (d, J=1.71 Hz, 1H) 7.67 (d, J=8.56 Hz, 2H) 7.80 (br. s, 1H) 7.87-7.99 (m, 2H) 8.04 (d, J=2.45 Hz, 1H) 8.74 (br. s, 1H) 10.28 (s, 1H) 12.76-13.20 (m, 1H).

Workup

  1. customto afford a pale yellow powder

Sources & evidence

ORD record
ord-39331114c4f648b991cfc3e1c737a52f
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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