Cesium carbonate → (r)-4-(4,5-Dimethyl-6-pyridin-2-ylmethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl-5'-carboxylic acid methyl ester

HRID 447093Notes

Reaction equation

HRID 447093 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[N:18]=[N:19][C:20](Cl)=[C:21]([CH3:24])[C:22]=3[CH3:23])[CH2:13][C@H:12]2[CH3:26])=[N:9][CH:10]=1)=[O:4].CC(C([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)(O)C(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[O-]S(C(F)(F)F)(=O)=O.[Pd+2].[O-]S(C(F)(F)F)(=O)=O.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[N:18]=[N:19][C:20]([CH2:35][C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=4)=[C:21]([CH3:24])[C:22]=3[CH3:23])[CH2:13][C@H:12]2[CH3:26])=[N:9][CH:10]=1)=[O:4]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 161262742,4-Dimethyl-3-pyridin-2-ylmethyl-pentan-3-olHCID 59191626(R)-4-(6-Chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H [1,2']bipyrazinyl-5'-carboxylic acid methyl ester

Product 1

HCID 59191517(r)-4-(4,5-Dimethyl-6-pyridin-2-ylmethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl-5'-carboxylic acid methyl esterYield 5.4%

Reagents, catalysts & solvents 2

HCID 11603820Palladium triflateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

(R)-4-(6-Chloro-4,5-dimethyl-pyridazin-3-yl)-2-methyl-3,4,5,6-tetrahydro-2H[1,2′]bipyrazinyl-5′-carboxylic acid methyl ester (250 mg, 0.663 mmol) is combined with 2,4-dimethyl-3-pyridin-2-ylmethyl-pentan-3-ol (114.6 mg, 0.553 mmol), cesium carbonate (216.2 mg, 0.664 mmol), palladium triflate (6.2 mg, 0.028 mmol), tricyclohexyl phosphine (15.5 mg, 0.055), and toluene (2 mL). The reaction mixture is heated to 110° C. for 65 h to reach 10% conversion. Add H2O and extract with EtOAc. Concentrate combined organics in vacuo. The residue is purified by flash chromatography on silica gel (MeOH/CH2Cl2) to afford the title compound (13 mg, 5.4%).

Workup

  1. extractionAdd H2O and extract with EtOAc
  2. concentrationConcentrate
  3. customThe residue is purified by flash chromatography on silica gel (MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-f613675d2636445ab55f4b268d0c7e89
Source dataset
uspto-grants-2013_07
Patent number
US08481542B2

Reaction notes

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