Water → N-(4-(6-chloropyrazin-2-ylthio)phenyl)cyclopropanecarboxamide

HRID 16196

Reaction equation

HRID 16196 reaction equation
[SH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH:11]2[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].[Cl:16][C:17]1[CH:22]=[N:21][CH:20]=[C:19](Cl)[N:18]=1.O>C1COCC1.C(OCC)(=O)C>[Cl:16][C:17]1[N:18]=[C:19]([S:1][C:2]2[CH:3]=[CH:4][C:5]([NH:8][C:9]([CH:11]3[CH2:12][CH2:13]3)=[O:10])=[CH:6][CH:7]=2)[CH:20]=[N:21][CH:22]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 785042,6-DichloropyrazineHCID 16722082N-(4-mercaptophenyl)cyclopropanecarboxamide

Product 1

HCID 59343401N-(4-(6-chloropyrazin-2-ylthio)phenyl)cyclopropanecarboxamideYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(4-mercaptophenyl)cyclopropane carboxamide (16.1 mmol) in THF (25 mL) at 0° C. was added sodium hydride (16.1 mmol) portionwise. Once the addition was complete the resulting solution was stirred at room temperature for 30 min. After this time, the reaction mixture was cooled to 0° C. and a solution of 2,6-dichloropyrazine (13.4 mmol) was added and the resulting mixture stirred at room temperature for 16 h. Water (30 mL) and ethyl acetate (30 mL) were added and the layers separated. The aqueous layer was extracted further with ethyl acetate (2×30 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) to give the title compound (2.95 g, 72%) as a cream coloured solid; 1H NMR (400 MHz, DMSO-d6) δ 0.91 (2H, m), 1.13 (2H, m), 1.54 (1H, m), 7.53 (1H, br s), 7.57 (2H, m), 7.65 (2H, m), 7.96 (1H, s), 8.22 (1H, s); MS (ES+): m/e=306.14 (100%).

Workup

  1. additionOnce the addition
  2. temperatureAfter this time, the reaction mixture was cooled to 0° C.
  3. stirringthe resulting mixture stirred at room temperature for 16 h
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted further with ethyl acetate (2×30 mL)
  6. dry with materialthe combined organic layers dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (EtOAc/Petroleum ether, 0-100% gradient EtOAc)

Sources & evidence

ORD record
ord-828b4a785b5f43c68f2fdae5541d9a91
Source dataset
uspto-grants-2010_06
Patent number
US07737151B2

Linked notes

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