Sodium Carbonate → (S)-ethyl 2-(6'-(benzyloxy)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-[3,3'-bipyridin]-5-yl)-2-(tert-butoxy)acetate

HRID 718340Notes

Reaction equation

HRID 718340 reaction equation
Br[C:2]1[C:3]([N:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)=[C:4]([C@H:10]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:5]([CH3:9])=[N:6][C:7]=1[CH3:8].[CH2:29]([O:36][C:37]1[N:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:29]([O:36][C:37]1[N:42]=[CH:41][C:40]([C:2]2[C:7]([CH3:8])=[N:6][C:5]([CH3:9])=[C:4]([C@H:10]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:3]=2[N:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)=[CH:39][CH:38]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177502166-Benzyloxypyridine-3-boronic acidHCID 118314215Ethyl (S)-2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118336859(S)-ethyl 2-(6'-(benzyloxy)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-[3,3'-bipyridin]-5-yl)-2-(tert-butoxy)acetateYield 24%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (0.0553 g, 0.121 mmol), (6-(benzyloxy)pyridin-3-yl)boronic acid (0.042 g, 0.182 mmol) and 2M Na2CO3 (0.152 ml, 0.304 mmol) in DMF (2 mL) was degassed for 10 min. Then, Pd(Ph3P)4 (0.014 g, 0.012 mmol) added, degassed for 5 min and placed in a pre-heated oil bath at 110° C. After 2 h, cooled and purified by prep-HPLC to afford (S)-ethyl 2-(6′-(benzyloxy)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-[3,3′-bipyridin]-5-yl)-2-(tert-butoxy)acetate (0.016 g, 0.029 mmol, 23.54% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 8.08-8.10 (m, 0.5H), 8.00 (d, J=1.9 Hz, 0.5H), 7.51-7.54 (m, 2.5H), 7.39-7.44 (m, 2.5H), 7.34-7.38 (m, 1H), 6.92-6.96 (m, 1H), 6.05 (s, 1H), 5.41-5.55 (m, 2H), 4.23-4.30 (m, 1H), 4.15-4.22 (m, 1H), 3.26 (d, J=12.3 Hz, 0.5H), 3.19 (d, J=11.5 Hz, 0.5H), 2.87-2.96 (m, 0.5H), 2.75-2.83 (m, 0.5H), 2.63 (s, 1.5H), 2.62 (s, 1.5H), 2.38 (d, J=11.2 Hz, 0.5H), 2.26-2.31 (m, 0.5H), 2.25 (s, 1.5H), 2.23 (s, 1.5H), 2.05-2.18 (m, 1H), 1.50-1.57 (m, 1H), 1.35-1.44 (m, 1H), 1.27 (dt, J=2.2, 7.1 Hz, 3H), 1.22 (s, 4.5H), 1.21 (s, 4.5H), 1.06-1.16 (m, 2H), 0.92 (s, 3H), 0.67 (br. s., 3H). LCMS (M+H)=560.4.

Workup

  1. customwas degassed for 10 min
  2. customdegassed for 5 min
  3. customplaced in a pre-heated oil bath at 110° C
  4. temperaturecooled
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-d09bd005cef44433963a7fe130ff90af
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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