1,2-Dimethoxyethane → 1-Methyl-1H-pyrazole-4-sulfonic acid {2-[3'-(4-cyanomethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochloride

HRID 553509Notes

Reaction equation

HRID 553509 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.COCCOC.[C:33]([CH2:35][C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)#[N:34].C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.O.C(OCC)(=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>[ClH:1].[C:33]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:2]2[C:3]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:26])[S:17]([C:20]4[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=4)(=[O:19])=[O:18])[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:38][CH:37]=1)#[N:34]

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27733424-(Cyanomethyl)benzeneboronic acidHCID 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 673688301-Methyl-1H-pyrazole-4-sulfonic acid {2-[3'-(4-cyanomethyl-phenyl)-2,3,5,6-tetrahydro-[1,2']bipyrazinyl-4-yl]-ethyl}-methyl-amide hydrochlorideYield 71%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 21534740N,N-Dimethylacetamide--water (1/1)Solvent

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 (0.250 g, 0.625 mmol) in DMA-H2O (or DME:H2O) (6 mL; 3:1 v/v, previously degassed with nitrogen). Add 4-cyanomethylphenyl boronic acid (0.121 g, 0.750 mmol), potassium carbonate (0.207 g, 1.500 mmol) and tetrakis(triphenylphosphine)palladium (0.036 g, 0.031 mmol). Stir 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. Dry the combined organic layers over sodium sulfate, filter, and concentrate. Purify by SCX chromatography, eluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol. Purify by silica gel chromatography eluting with hexanes:acetone 1:1 to afford the free base of the title compound (0.214 g, 71% yield).

Workup

  1. custom3:1 v/v, previously degassed with nitrogen)
  2. temperatureCool
  3. extractionExtract the aqueous layer with ethyl acetate
  4. dry with materialDry the combined organic layers over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by SCX chromatography
  8. washeluting with dichloromethane, dichloromethane:methanol 1:1, methanol, and 1N ammonia in methanol
  9. customPurify by silica gel chromatography
  10. washeluting with hexanes:acetone 1:1

Sources & evidence

ORD record
ord-acf2e4662d2345d7b20de649db1d2f69
Source dataset
uspto-grants-2011_11
Patent number
US08048884B2

Reaction notes

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