1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (R)-N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1-methyl-1H-pyrazol-3-yl)nicotinamide

HRID 73793

Reaction equation

HRID 73793 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]([O:16][C:17]([Cl:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[CH3:28][N:29]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[N:30]1>>[Cl:20][C:17]([F:19])([F:18])[O:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:21]=[C:2]([C:31]3[CH:32]=[CH:33][N:29]([CH3:28])[N:30]=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 27600771-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 72545856(R)-5-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide

Product 1

HCID 72545602(R)-N-(4-(Chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)-5-(1-methyl-1H-pyrazol-3-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Stage 2.1 using (R)-5-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxypyrrolidin-1-yl)nicotinamide (Stage 9.2) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole to afford a white powder. HPLC (Condition 4) tR=5.16 min, UPLC-MS (Condition 3) tR0.98 min, m/z=464 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.64-1.90 (m, 2H) 2.85-3.00 (m, 1H) 3.06-3.26 (m, 3H) 3.59 (s, 3H) 4.19 (br. s, 1H) 4.87 (d, J=2.74 Hz, 1H) 6.39 (s, 1H) 7.31 (d, J=8.60 Hz, 2H) 7.50 (dd, J=1.76, 0.98 Hz, 1H) 7.84 (d, J=8.60 Hz, 2H) 8.01 (d, J=2.74 Hz, 1H) 8.78 (dd, J=2.54, 0.98 Hz, 1H) 10.15 (s, 1H).

Workup

  1. customto afford a white powder

Sources & evidence

ORD record
ord-e7826718383b4bdd95100c8806294036
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Linked notes

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