Cyclopropanecarbonyl chloride → HCID 178521770, compound

HRID 2282159Notes

Reaction equation

HRID 2282159 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=3)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:24]1([C:27](Cl)=[O:28])[CH2:26][CH2:25]1.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[C:1]1([C:7]2[N:8]=[C:9]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:27]([CH:24]4[CH2:26][CH2:25]4)=[O:28])[CH:18]=3)[S:10][C:11]=2[C:12]2[NH:16][CH:15]=[N:14][N:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 77637Cyclopropanecarbonyl chloride2×HCID 516892Sodium BicarbonateHCID 178507331HCID 178507331, compound

Product 1

HCID 178521770HCID 178521770, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A mixture of 4-[4-phenyl-5-(4H-1,2,4-triazol-3-yl)-1,3-thiazol-2-yl]pyridin-2-amine (150 mg, 0.47 mmol) produced in Example 2-B, cyclopropanecarbonyl chloride (0.13 mL, 1.40 mmol) and pyridine (5 mL) was stirred at room temperature for 6 hr. To the reaction mixture was added cyclopropanecarbonyl chloride (0.085 mL, 0.94 mmol) and the mixture was stirred at room temperature for 1 day. To the reaction mixture was added aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→100/0), and 1N aqueous sodium hydroxide solution (0.5 mL), methanol (5 mL) and tetrahydrofuran (10 mL) were added to the crude product. The mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and water was added to the obtained residue. After neutralization with 1N hydrochloric acid, the resulting precipitate was collected by filtration, washed with water and diethyl ether and dried to give the title compound (145 mg, 80%) as a pale-yellow solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 day
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationthe insoluble material was filtered off
  6. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→100/0), and 1N aqueous sodium hydroxide solution (0.5 mL), methanol (5 mL) and tetrahydrofuran (10 mL)
  7. additionwere added to the crude product
  8. stirringThe mixture was stirred at room temperature for 1 hr
  9. concentrationThe reaction mixture was concentrated under reduced pressure, and water
  10. additionwas added to the obtained residue
  11. filtrationAfter neutralization with 1N hydrochloric acid, the resulting precipitate was collected by filtration
  12. washwashed with water and diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-6048301beeb248fabdec464f57fcbf6b
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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