Acetone → N-[4-(4-{2-[Methyl-(1-methyl-1H-pyrazole-4-sulfonyl)-amino]-ethyl}-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-benzyl]-acetamide hydrochloride

HRID 553513Notes

Reaction equation

HRID 553513 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]3[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=3)(=[O:19])=[O:18])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.C(N[C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)(=O)C.C(=O)([O-])[O-].[K+].[K+].CC(C)=O.[CH3:50][C:51]([N:53](C)[CH3:54])=[O:52].O>C(OCC)(=O)C.O>[ClH:1].[CH3:26][N:16]([S:17]([C:20]1[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=1)(=[O:19])=[O:18])[CH2:15][CH2:14][N:11]1[CH2:12][CH2:13][N:8]([C:3]2[C:2]([C:31]3[CH:32]=[CH:33][C:34]([CH2:54][NH:53][C:51](=[O:52])[CH3:50])=[CH:35][CH:36]=3)=[N:7][CH:6]=[CH:5][N:4]=2)[CH2:9][CH2:10]1

Participants

8

Reactant 5

HCID 180AcetoneHCID 11430Potassium CarbonateHCID 27346574-Acetamidophenylboronic acidHCID 21534740N,N-Dimethylacetamide--water (1/1)HCID 866402031-Methyl-1H-pyrazole-4-sulfonic acid [2-(3'-chloro-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl)-ethyl]-methyl-amide

Product 1

HCID 67366252N-[4-(4-{2-[Methyl-(1-methyl-1H-pyrazole-4-sulfonyl)-amino]-ethyl}-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl)-benzyl]-acetamide hydrochlorideYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Dissolve 1-methyl-1H-pyrazole-4-sulfonic acid [2-(3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-yl)-ethyl]-methyl-amide (200 mg, 0.483 mmol) in DMA-H2O (10 ml; 3:1 v/v, previously degassed with nitrogen). Add 4-acetamidophenyl boronic acid (112 mg, 0.580 mmol), potassium carbonate (160 mg, 1.16 mmol) and tetrakis(triphenyl-phosphine)palladium (28 mg, 0.024 mmol). Heat the reaction mixture at 110° C. for 18 hr. Cool and dilute with ethyl acetate and water. Extract the aqueous layer with ethyl acetate and combine the organic layers. Wash the combined organic layers with brine and concentrate. Purify by chromatography, eluting with 1:2 hexanes:acetone to afford the free base of the title compound (124 mg, 50% yield) as a white foam.

Workup

  1. custom3:1 v/v, previously degassed with nitrogen)
  2. temperatureCool
  3. extractionExtract the aqueous layer with ethyl acetate
  4. washWash the combined organic layers with brine
  5. concentrationconcentrate
  6. customPurify by chromatography
  7. washeluting with 1:2 hexanes

Sources & evidence

ORD record
ord-91cc292e872b43b3bb3e68b1a3c106ad
Source dataset
uspto-grants-2011_11
Patent number
US08048884B2

Reaction notes

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