Sodium Carbonate → HCID 178428276, compound

HRID 1668652Notes

Reaction equation

HRID 1668652 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])=[CH:11][CH:10]=2)[CH:5]=[N:4][CH:3]=1.[NH2:21][C:22]1[CH:26]=[C:25]([CH3:27])[NH:24][N:23]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(OCC)(=O)C.O>[CH3:27][C:25]1[CH:26]=[C:22]([NH:21][C:2]2[N:7]=[C:6]([S:8][C:9]3[CH:14]=[CH:13][C:12]([NH:15][C:16]([CH:18]4[CH2:20][CH2:19]4)=[O:17])=[CH:11][CH:10]=3)[CH:5]=[N:4][CH:3]=2)[NH:23][N:24]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59343401N-(4-(6-chloropyrazin-2-ylthio)phenyl)cyclopropanecarboxamide

Product 1

HCID 178428276HCID 178428276, compoundYield 6%

Reagents, catalysts & solvents 4

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of N-(4-(6-chloropyrazin-2-ylthio)phenyl)cyclopropanecarboxamide (0.49 mmol) and 3-amino-5-methylpyrazole (0.52 mmol) in 1,4-dioxan (3 mL), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.03 mmol), tris(dibenzylideneacetone) dipalladium (0.02 mmol) and sodium carbonate (0.69 mmol) were added. The resulting solution was heated at 120° C. in the microwave (175 W, 25 psi) for 30 min. Water (10 mL) and ethyl acetate (10 mL) were added and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×10 mL), the combined organic layers dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/Petroleum ether, 0-100% gradient EtOAc) and then purified further using mass directed HPLC purification (sunfire C18 column, trifluoroacetic acid/MeCN/MeOH as eluent) to give the title compound (10.6 mg, 6%) as a light yellow solid; 1H NMR (400 MHz, DMSO-d6) δ 0.81 (4H, m), 1.83 (1H, m), 2.05 (3H, s), 5.55 (1H, s), 7.54 (2H, m), 7.59 (1H, s), 7.74 (2H, m), 8.02 (1H, s), 9.77 (1H, s), 10.47 (1H, s); MS (ES+): m/e=367.41 (100%).

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted further with ethyl acetate (2×10 mL)
  3. dry with materialthe combined organic layers dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (EtOAc/Petroleum ether, 0-100% gradient EtOAc)
  6. custompurified further
  7. customHPLC purification (sunfire C18 column, trifluoroacetic acid/MeCN/MeOH as eluent)

Sources & evidence

ORD record
ord-c1b806b52f3c4557911432f01e29e7c1
Source dataset
uspto-grants-2011_08
Patent number
US07989456B2

Reaction notes

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