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

HRID 73776Notes

Reaction equation

HRID 73776 reaction equation
Br[C:2]1[C:3]([N:25]2[CH2:29][CH2:28][C@@H:27]([OH:30])[CH2:26]2)=[N:4][CH:5]=[C:6]([CH:24]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:23])([F:22])[C:18]([F:21])([F:20])[F:19])=[CH:12][CH:11]=1)=[O:8].O1CCCCC1[N:37]1[C:41](B2OC(C)(C)C(C)(C)O2)=[CH:40][CH:39]=[N:38]1>>[OH:30][C@@H:27]1[CH2:28][CH2:29][N:25]([C:3]2[C:2]([C:39]3[NH:38][N:37]=[CH:41][CH:40]=3)=[CH:24][C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:23])([F:22])[C:18]([F:20])([F:19])[F:21])=[CH:12][CH:11]=3)=[O:8])=[CH:5][N:4]=2)[CH2:26]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 86702619(R)-5-bromo-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(perfluoroethoxy)phenyl)nicotinamide

Product 1

HCID 72544892(R)-6-(3-Hydroxypyrrolidin-1-yl)-N-(4-(perfluoroethoxy)phenyl)-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-6-(3-hydroxypyrrolidin-1-yl)-N-(4-(perfluoroethoxy)phenyl)nicotinamide (Stage 19.1) 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=4.86 min, UPLC-MS (Condition 3) tR=0.97 min, m/z=484.4 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.62-1.92 (m, 2H) 2.94 (d, J=1.00 Hz, 1H) 3.18-3.34 (m, 2H) 3.37-3.51 (m, 1H) 4.13-4.22 (m, 1H) 4.70-4.91 (m, 1H) 6.37 (br. s, 1H) 7.31 (d, J=8.99 Hz, 2H) 7.86 (m, J=9.00 Hz, 3H) 8.01 (br. s, 1H) 8.65-8.83 (m, 1H) 10.17 (s, 1H) 12.84-13.11 (m, 1H).

Workup

  1. customto afford an off-white solid

Sources & evidence

ORD record
ord-388451dd97764f5b8a1ff5c96e17ac59
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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