Hydrochloric Acid → 3-tert-butyl-N-(2-(5-(3-chloro-4-cyano-2-methylphenyl)furan-2-yl)ethyl)-1H-pyrazole-5-carboxamide

HRID 872537

Reaction equation

HRID 872537 reaction equation
N[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([Cl:10])[C:3]=1[CH3:11].Cl.N([O-])=O.[Na+].[C:17]([C:21]1[CH:25]=[C:24]([C:26]([NH:28][CH2:29][CH2:30][C:31]2[O:32][CH:33]=[CH:34][CH:35]=2)=[O:27])[NH:23][N:22]=1)([CH3:20])([CH3:19])[CH3:18]>O.CC(C)=O.O.O.O.O.[Fe](Cl)Cl>[C:17]([C:21]1[CH:25]=[C:24]([C:26]([NH:28][CH2:29][CH2:30][C:31]2[O:32][C:33]([C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([Cl:10])[C:3]=3[CH3:11])=[CH:34][CH:35]=2)=[O:27])[NH:23][N:22]=1)([CH3:20])([CH3:18])[CH3:19]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 218754134-Amino-2-chloro-3-methylbenzonitrileHCID 23668193Sodium NitriteHCID 1784410803-tert-butyl-N-(2-(furan-2-yl)-ethyl)-1H-pyrazole-5-carboxamide

Product 1

HCID 1784219593-tert-butyl-N-(2-(5-(3-chloro-4-cyano-2-methylphenyl)furan-2-yl)ethyl)-1H-pyrazole-5-carboxamideYield 2.6%

Reagents, catalysts & solvents 3

HCID 16211588Ferrous chloride tetrahydrateCatalystHCID 180AcetoneSolventHCID 962WaterSolvent4×

Conditions

Temperature
80 °C

Procedure

4-amino-2-chloro-3-methylbenzonitrile (0.200 g, 1.20 mmol) was added to a solution of water (2 ml) and conc. HCl (2 ml) and the mixture was stirred vigorously, heated to 80° C. for 15 min and then cooled to −10° C. Sodium nitrite (0.091 g, 1.32 mmol) was dissolved in 0.5 ml of water and added drop wise to the cooled reaction mixture. After 40 min, the mixture was filtered and 3-tert-butyl-N-(2-(furan-2-yl)-ethyl)-1H-pyrazole-5-carboxamide (0.345 g, 1.32 mmol) dissolved in acetone (3 ml) was added to the filtrate. Then, a solution of iron (II) chloride tetrahydrate in water (3 ml) was added portion wise and the mixture was stirred for 15 h at RT. Water (25 ml) was added to the reaction mixture and extracted three times with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO3 and water and dried with Na2SO4, filtered and evaporated to dryness. CombiFlash purification afforded 0.013 g of the title compound. 1H-NMR (400 MHz; d6-DMSO): δ 1.34 (s, 9H), 3.03 (t, 2H), 3.77 (m, 2H), 6.28 (d, 1H), 6.62 (m, 2H), 7.12 (m, 1H), 7.50 (d, 1H), 7.65 (d, 1H).

Workup

  1. temperaturecooled to −10° C
  2. additionadded drop
  3. customwise to the cooled reaction mixture
  4. filtrationthe mixture was filtered
  5. additionwas added to the filtrate
  6. stirringthe mixture was stirred for 15 h at RT
  7. extractionextracted three times with EtOAc
  8. washThe combined organic layers were washed with saturated aqueous NaHCO3 and water
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered
  11. customevaporated to dryness
  12. customCombiFlash purification

Sources & evidence

ORD record
ord-69754be82c7c477e94d23066f3fe62a7
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Linked notes

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