(Pyrimidin-5-yl)boronic acid → (S)-N-(3-Fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinamide

HRID 924060Notes

Reaction equation

HRID 924060 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].[N:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32][CH:31]=1>>[F:21][C:12]1[CH:11]=[C:10]([NH:9][C:7](=[O:8])[C:6]2[CH:22]=[C:2]([C:34]3[CH:35]=[N:30][CH:31]=[N:32][CH:33]=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 2795193(Pyrimidin-5-yl)boronic acidHCID 86702609(S)-5-bromo-N-(3-fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide

Product 1

HCID 118195336(S)-N-(3-Fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)-5-(pyrimidin-5-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 185 using (S)-5-bromo-N-(3-fluoro-4-(trifluoromethoxy)phenyl)-6-(3-(hydroxymethyl)pyrrolidin-1-yl)nicotinamide (Stage 201.1) and pyrimidin-5-ylboronic acid to afford a white powder. HPLC (Condition 4) tR=4.98 min, UPLC-MS (Condition 3) tR=0.97 min, m/z=478.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.50-1.65 (m, 1H) 1.84 (m, J=6.60 Hz, 1H) 2.15-2.29 (m, 1H) 2.96 (dd, J=10.75, 6.84 Hz, 1H) 3.06-3.42 (m, 5H) 4.60 (t, J=5.28 Hz, 1H) 7.47-7.64 (m, 2H) 7.96 (dd, J=13.10, 2.15 Hz, 1H) 8.06 (d, J=2.35 Hz, 1H) 8.77 (d, J=2.74 Hz, 1H) 8.84-8.94 (m, 2H) 9.17 (s, 1H) 10.29 (s, 1H).

Workup

  1. customto afford a white powder

Sources & evidence

ORD record
ord-34685ae61db7414bb4bb755bc0e79aee
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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