Cesium carbonate → HCID 118314222, compound

HRID 718365Notes

Reaction equation

HRID 718365 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].[F:29][C:30]1[CH:47]=[CH:46][C:33]([CH2:34][CH2:35][O:36][C:37]2[N:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=2)=[CH:32][CH:31]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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>[C:17]([O:16][C@@H:10]([C:4]1[C:3]([N:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)=[C:2]([C:40]2[CH:41]=[N:42][C:37]([O:36][CH2:35][CH2:34][C:33]3[CH:32]=[CH:31][C:30]([F:29])=[CH:47][CH:46]=3)=[CH:38][CH:39]=2)[C:7]([CH3:8])=[N:6][C:5]=1[CH3:9])[C:11]([O:13][CH2:14][CH3:15])=[O:12])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 118314215Ethyl (S)-2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetateHCID 123507232HCID 123507232, compound

Product 1

HCID 118314222HCID 118314222, compoundYield 9.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of (S)-ethyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (30 mg), (6-(4-fluorophenethoxy)pyridin-3-yl)boronic acid (18.9 mg) and Cs2CO3 (42.9 mg) in 1,4-dioxane (2 mL) and water (0.4 mL) was added Pd(PPh3)4 (7.6 mg). The mixture was flushed with nitrogen and then heated at 85° C. for 3 h. The mixture was diluted with water and then extracted with EtOAc (2×20 mL). The organic layers were combined, washed with brine and concentrated to give a residue, which was purified by the preparative HPLC to give (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-6′-(4-fluorophenethoxy)-2,6-dimethyl-[3,3′-bipyridin]-5-yl)acetate (3.6 mg). LCMS (M+H)=592.5.

Workup

  1. customThe mixture was flushed with nitrogen
  2. additionThe mixture was diluted with water
  3. extractionextracted with EtOAc (2×20 mL)
  4. washwashed with brine
  5. concentrationconcentrated
  6. customto give a residue, which
  7. customwas purified by the preparative HPLC

Sources & evidence

ORD record
ord-a44c6e0ff3bf45a2a898336e5b171110
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

Loading…