Hydrochloric Acid → N-(2-{4-[4-(1,5-Dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenyl}-ethyl)-methanesulfonamide hydrochloride

HRID 220586Notes

Reaction equation

HRID 220586 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]([CH3:21])[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[C:22](=O)([O-])[O-].[K+].[K+].[S:28](=[N:31][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1)(=[O:30])=[O:29].Cl>CN(C)C(=O)C.C(#N)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.O>[ClH:1].[CH3:21][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][CH2:32][NH:31][S:28]([CH3:22])(=[O:30])=[O:29])=[CH:35][CH:36]=4)=[N:7][CH:6]=[CH:5][N:4]=3)[CH2:9][CH2:10]2)[CH:16]=[N:17]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 594382163'-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinylHCID 866416664-Sulfonylaminoethyl benzene boronic acid

Product 1

HCID 68595086N-(2-{4-[4-(1,5-Dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenyl}-ethyl)-methanesulfonamide hydrochlorideYield 72.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

Dissolve 3′-chloro-4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (307 mg, 1.0 mmol) in N,N-dimethylacetamide (4 mL). Add potassium carbonate (331 mg, 2.4 mmol), 4-sulfonylaminoethyl benzene boronic acid (292 mg, 1.2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.0050 g, 0.0058 mmol), then water (2 mL) and degas with nitrogen for 10 min. Heat at 120° C. for 20 hr., then purify by SCX-2® chromatography washing with methanol. Elute with 2 M ammonia in methanol and concentrate. Recrystallize from DMSO:methanol (1:1), filter and wash with diethyl ether, to give a whitish powder. Dissolve the powder in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a yellow powder (365 mg, 71%). MS (ES): m/z=470 [M+H]+.

Workup

  1. custom, then purify by SCX-2® chromatography
  2. washwashing with methanol
  3. washElute with 2 M ammonia in methanol
  4. concentrationconcentrate
  5. customRecrystallize from DMSO:methanol (1:1)
  6. filtrationfilter
  7. washwash with diethyl ether
  8. customto give a whitish powder

Sources & evidence

ORD record
ord-3dba0c0aec6e45e291741f492d990baf
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…