4-Cyanophenylboronic acid → HCID 68736154, compound

HRID 220428Notes

Reaction equation

HRID 220428 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19](Cl)=[N:18][CH:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)#[N:22]>CN(C)C(=O)C.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:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([C:26]3[CH:27]=[CH:28][C:23]([C:21]#[N:22])=[CH:24][CH:25]=3)=[N:18][CH:17]=[CH:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 27343264-Cyanophenylboronic acidHCID 11150691Tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate

Product 1

HCID 68736154HCID 68736154, compoundYield 88.3%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

Dissolve 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (9.19 g, 30.8 mmol) and 4-cyanobenzeneboronic acid (5.18 g, 35.2 mmol) in N,N-dimethylacetamide (90 mL) and water (35 mL), purge with nitrogen for 0.5 hr. and then add tetrakis(triphenylphosphine)palladium(0) (0.170 g, 0.15 mmol). Heat for 3 hr. at 110° C., allow to cool about 1.5 hr. to room temperature, filter and then dry the solid in an oven overnight to give 3′-(4-cyanophenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester as a white solid (9.94 g, 88%). MS (ES): m/z=366 [M+H]+. Add 4 M HCl in 1,4-dioxane (10 mL) to 3′-(4-cyanophenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (3.29 g, 9.0 mmol). Add more 4 M HCl in 1,4-dioxane (10 mL) to the reaction mixture and heat at 40° C. for 3 hr. Filter off the solid and wash with a mixture of 1,4-dioxane/isohexane to give the dihydrochloride salt as a yellow solid (4.2 g). MS (ES): m/z=266 [M+H]+. Dissolve the dihydrochloride in water (20 mL), add 2 N sodium hydroxide (10 mL), extract with DCM and concentrate the DCM extract to give the title preparation as a yellow solid (1.8 g). MS (ES): m/z=266 [M+H]+.

Workup

  1. custompurge with nitrogen for 0.5 hr
  2. temperatureHeat for 3 hr
  3. customat 110° C.
  4. temperatureto cool about 1.5 hr
  5. filtrationto room temperature, filter
  6. customdry the solid in an oven overnight

Sources & evidence

ORD record
ord-dbd28346cf234522b8c2a215d44f567b
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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