1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → (R)-N-(4-(Chlorodifluoromethoxy)phenyl)-4-(3-hydroxypyrrolidin-1-yl)-3-(1H-pyrazol-5-yl)benzamide

HRID 73779Notes

Reaction equation

HRID 73779 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N:22]1[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([Cl:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].O1CCCCC1[N:34]1[C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][CH:36]=[N:35]1>>[Cl:18][C:15]([F:17])([F:16])[O:14][C:11]1[CH:12]=[CH:13][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:19]=[CH:20][C:21]([N:22]3[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]3)=[C:2]([C:36]3[NH:35][N:34]=[CH:38][CH:37]=3)[CH:3]=2)=[CH:9][CH:10]=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 86702621(R)-3-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-(3-hydroxypyrrolidin-1-yl)benzamide

Product 1

HCID 72544442(R)-N-(4-(Chlorodifluoromethoxy)phenyl)-4-(3-hydroxypyrrolidin-1-yl)-3-(1H-pyrazol-5-yl)benzamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 8 using (R)-3-bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-(3-hydroxypyrrolidin-1-yl)benzamide (Stage 20.1) and 1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole-5-boronic acid pinacol ester to afford an off-white solid. UPLC-MS (Condition 3) tR=0.99 min, m/z=449.0 [M+H]+, m/z=493.0 [M+formic acid-H]−; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.67-1.79 (m, 1H) 1.80-1.92 (m, 1H) 2.72 (d, J=10.88 Hz, 1H) 3.03-3.18 (m, 2H) 3.19-3.30 (m, 1H) 4.19 (br. s, 1H) 4.77-4.92 (m, 1H) 6.22-6.42 (m, 1H) 6.76-6.93 (m, 1H) 7.31 (d, J=8.56 Hz, 2H) 7.45-7.81 (m, 1H) 7.83-7.95 (m, 4H) 10.12 (s, 1H) 12.71-13.12 (m, 1H).

Workup

  1. customto afford an off-white solid

Sources & evidence

ORD record
ord-937151d7f9f4407781f90c1134fdfa4f
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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