2-Aminothiazole → HCID 10380414, compound

HRID 1816123Notes

Reaction equation

HRID 1816123 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:13]([OH:15])=O)=[CH:7][N:8]2[CH2:11][CH3:12])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[S:24][CH:25]=[CH:26][N:27]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C)C=O>[S:24]1[CH:25]=[CH:26][N:27]=[C:23]1[NH:22][C:13]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:8]([CH2:11][CH3:12])[CH:7]=1)=[O:15]

Participants

8

Reactant 4

HCID 21552-AminothiazoleHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 22497244HCID 22497244, compound

Product 1

HCID 10380414HCID 10380414, compoundYield 8.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-chloro-1-ethyl-1H-indole-3-carboxylic acid (240 mg, 1.07 mmol) in methylene chloride (3 mL) was cooled to 0° C. and then treated with N,N-dimethylformamide (1 drop) and oxalyl chloride (0.14 mL, 1.61 mmol). The reaction was stirred at 0° C. for 15 min and then was allowed to warm to 25° C. where it was stirred for 1 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in methylene chloride (1 mL), and this mixture was then added to a solution of 2-aminothiazole (214 mg, 2.14 mmol) and triethylamine (0.30 mL, 2.14 mmol) in N,N-dimethylformamide (2 mL). This mixture was stirred at 25° C. for 16 h. At this time, the reaction was partitioned between water (40 mL) and ethyl acetate (40 mL). This mixture was then treated with a 1N aqueous hydrochloric acid solution (15 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×30 mL), water (1×30 mL), and a saturated aqueous sodium chloride solution (1×30 mL). The organic layer was then dried over magnesium sulfate, filtered, and concentrated in vacuo. Recrystallization from ethyl acetate afforded 6-chloro-1-ethyl-1H-indole-3-carboxylic acid thiazol-2-ylamide (27 mg, 8%) as a pale yellow solid: mp 234-236° C.; EI-HRMS m/e calcd for C14H12ClN3OS (M+) 305.0390, found 305.0383.

Workup

  1. temperatureto warm to 25° C. where it
  2. stirringwas stirred for 1 h
  3. concentrationAt this time, the reaction was concentrated in vacuo
  4. dissolutionThe residue was dissolved in methylene chloride (1 mL)
  5. stirringThis mixture was stirred at 25° C. for 16 h
  6. customAt this time, the reaction was partitioned between water (40 mL) and ethyl acetate (40 mL)
  7. additionThis mixture was then treated with a 1N aqueous hydrochloric acid solution (15 mL)
  8. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×30 mL), water (1×30 mL)
  9. dry with materialThe organic layer was then dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customRecrystallization from ethyl acetate

Sources & evidence

ORD record
ord-96449c73acfa49df826cf978400b56d2
Source dataset
uspto-grants-2005_04
Patent number
US06881844B2

Reaction notes

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