Water → N-{4-[4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochloride

HRID 220580Notes

Reaction equation

HRID 220580 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[N:17][N:18]([CH2:21][CH3:22])[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:29]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1)(=[O:31])[CH3:30].O>CN(C)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>[ClH:1].[CH2:21]([N:18]1[C:19]([CH3:20])=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:3]3[C:2]([C:37]4[CH:38]=[CH:39][C:34]([CH2:33][NH:32][C:29](=[O:31])[CH3:30])=[CH:35][CH:36]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1)[CH3:22]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 223094544-[(Acetylamino)methyl]benzeneboronic acidHCID 866416643'-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Product 1

HCID 68595359N-{4-[4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-benzyl}-acetamide hydrochlorideYield 95%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Procedure

Combine 3′-chloro-4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (0.300 g, 0.935 mmol), potassium carbonate (0.310 g, 2.24 mmol), (4-acetamidomethylphenyl)boronic acid (0.216 g, 1.12 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.011 g, 0.009 mmol) in N,N-dimethylacetamide (1.9 mL). Add water (940 μL), and reflux reaction for 6 hr. Add DCM and wash with water. Extract water layer three times with DCM. Dry combined organics (magnesium sulfate) and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate:hexanes then 10:90 to 20:80 methanol:ethyl acetate), to give the free base of the title compound (384 mg, 95%). Dissolve the free base (0.381 g, 0.880 mmol) in acetonitrile (1.06 mL) and add aq. 1 N HCl solution (1.06 mL, 1.06 mmol). Shake for 15 min. at ambient temperature. Freeze dry to give the title compound (416 mg, 100%). MS (ES): m/z=434 [M+H]+.

Workup

  1. customreaction for 6 hr
  2. washAdd DCM and wash with water
  3. customDry
  4. custompurify (silica gel chromatography
  5. washeluting with 50:50 to 100:0 ethyl acetate

Sources & evidence

ORD record
ord-deec3cbc1ce04a068b37209f3647e0cf
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…