Cesium carbonate → Methyl 5-{3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylate

HRID 571549Notes

Reaction equation

HRID 571549 reaction equation
Cl.[CH3:2][C:3]1([CH3:22])[C:7]([CH3:9])([CH3:8])[O:6][B:5]([C:10]2[CH:11]=[N:12][N:13]([C:15]3([CH2:19][C:20]#[N:21])[CH2:18][NH:17][CH2:16]3)[CH:14]=2)[O:4]1.Cl[C:24]1[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:20]([CH2:19][C:15]1([N:13]2[CH:14]=[C:10]([B:5]3[O:6][C:7]([CH3:8])([CH3:9])[C:3]([CH3:22])([CH3:2])[O:4]3)[CH:11]=[N:12]2)[CH2:16][N:17]([C:24]2[N:25]=[CH:26][C:27]([C:30]([O:32][CH3:33])=[O:31])=[N:28][CH:29]=2)[CH2:18]1)#[N:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 634876Binap, (A+-)-HCID 712080171416785-40-4Freebase

Product 1

HCID 71143602Methyl 5-{3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylateYield 53.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of {3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile HCl salt (400. mg, 1.23 mmol), methyl 5-chloropyrazine-2-carboxylate (223 mg, 1.29 mmol), cesium carbonate (800 mg, 2.5 mmol), palladium acetate (28 mg, 0.12 mmol) and (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (150 mg, 0.25 mmol) in toluene (5 mL) was stirred at 100° C. for 3 h. After the reaction mixture was cooled to room temperature, the solid was separated, and washed with ethyl acetate twice. The filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford the desired product (0.28 g). LCMS (M+H)+: m/z=425.2.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. customthe solid was separated
  3. washwashed with ethyl acetate twice
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)

Sources & evidence

ORD record
ord-3bd906b477c14550afa242df57837a98
Source dataset
uspto-grants-2015_05
Patent number
US09023840B2

Reaction notes

Loading…