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

HRID 73762Notes

Reaction equation

HRID 73762 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].O1CCCCC1[N:36]1[C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][CH:38]=[N:37]1>>[F:21][C:12]1[CH:11]=[C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:22]=[C:2]([C:38]3[NH:37][N:36]=[CH:40][CH:39]=3)[C:3]([N:23]3[CH2:27][CH2:26][C@H:25]([CH2:28][OH:29])[CH2:24]3)=[N:4][CH:5]=2)[CH:15]=[CH:14][C:13]=1[O:16][C:17]([F:20])([F:19])[F:18]

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 86702609(S)-5-bromo-N-(3-fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide

Product 1

HCID 72544889(S)-N-(3-Fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-5-(1H-pyrazol-5-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 10 using (S)-5-bromo-N-(3-fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide (Stage 14.1) 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=0.96 min, m/z=466.2 [M+H]+, m/z=464.2 [M−H]−. 1H-NMR (400 MHz, DMSO-d6) d ppm 2.77 (s, 3H) 3.38-3.61 (m, 4H) 4.61 (br. s, 1H) 6.47 (s, 1H) 7.68 (d, J=8.56 Hz, 2H) 7.83 (br. s, 1H) 7.93 (d, J=8.80 Hz, 2H) 8.15 (br. s, 1H) 8.71 (br. s, 1H) 10.36 (s, 1H) 12.83-13.15 (m, 1H).

Workup

  1. customto afford a pale yellow powder

Sources & evidence

ORD record
ord-97d7ae931e4f43738d15eb7ea90efac6
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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