2-Cyanopyrimidine-5-boronic acid pinacol ester → (S)-5-(2-Cyanopyrimidin-5-yl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 923903Notes

Reaction equation

HRID 923903 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]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].CC1(C)C(C)(C)OB([C:37]2[CH:38]=[N:39][C:40]([C:43]#[N:44])=[N:41][CH:42]=2)O1>>[C:43]([C:40]1[N:41]=[CH:42][C:37]([C:2]2[C:3]([N:22]3[CH2:26][CH2:25][C@H:24]([CH2:27][OH:28])[CH2:23]3)=[N:4][CH:5]=[C:6]([CH:21]=2)[C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]([F:19])([F:18])[F:20])=[CH:12][CH:11]=2)=[O:8])=[CH:38][N:39]=1)#[N:44]

Participants

3

Reactant 2

HCID 164142762-Cyanopyrimidine-5-boronic acid pinacol esterHCID 86702601(S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 118195283(S)-5-(2-Cyanopyrimidin-5-yl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 75 using (S)-5-bromo-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 78.1) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile to afford a yellow solid. UPLC-MS (condition 1) tR=2.54 min, m/z=485.0 [M+H]+, m/z=4831.1 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.55-1.67 (m, 1H) 1.82-1.93 (m, 1H) 2.21-2.30 (m, 1H) 2.98 (dd, J=11.00, 7.09 Hz, 1H) 3.14-3.30 (m, 4H) 3.33-3.41 (m, 1H) 4.62 (t, J=5.26 Hz, 1H) 7.36 (d, J=8.80 Hz, 2H) 7.85 (d, J=9.05 Hz, 2H) 8.17 (d, J=2.20 Hz, 1H) 8.82 (d, J=2.20 Hz, 1H) 9.10 (s, 2H) 10.20 (s, 1H).

Workup

  1. customto afford a yellow solid

Sources & evidence

ORD record
ord-9828954859dc42119ac5837404e5072f
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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