2-Aminothiazole → 6-bromo-1-isopropyl-1H-indole-3-carboxylic acid thiazol-2-ylamide

HRID 1816118Notes

Reaction equation

HRID 1816118 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Br:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([C:41]([OH:43])=O)=[CH:34][N:35]2[CH:38]([CH3:40])[CH3:39])=[CH:31][CH:30]=1.[NH2:44][C:45]1[S:46][CH:47]=[CH:48][N:49]=1>C(Cl)Cl>[S:46]1[CH:47]=[CH:48][N:49]=[C:45]1[NH:44][C:41]([C:33]1[C:32]2[C:36](=[CH:37][C:29]([Br:28])=[CH:30][CH:31]=2)[N:35]([CH:38]([CH3:39])[CH3:40])[CH:34]=1)=[O:43]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 224972346-bromo-1-isopropyl-1H-indole-3-carboxylic acid

Product 1

HCID 104288286-bromo-1-isopropyl-1H-indole-3-carboxylic acid thiazol-2-ylamideYield 11.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (2.42 mg, 9.22 mmol) in methylene chloride (25 mL) cooled to 0° C. was treated with N-bromosuccinimide (1.64 mg, 9.22 mmol). The reaction was stirred at 0° C. for 15 min. At this time, the reaction was treated with 6-bromo-1-isopropyl-1H-indole-3-carboxylic acid (2.0 g, 7.09 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 15 min. The reaction was then treated with 2-aminothiazole (1.63 g, 16.31 mmol) and stirred at 25° C. for 18 h. At this time, the mixture was partitioned between water (150 mL) and ethyl acetate (150 mL) and treated with a 1N aqueous hydrochloric acid solution (100 mL). The organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×100 mL), water (1×100 mL), and a saturated aqueous sodium chloride solution (1×100 mL). The organic layer was then dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 1/1 hexanes/ethyl acetate) afforded 6-bromo-1-isopropyl-1H-indole-3-carboxylic acid thiazol-2-ylamide (300 mg, 11.6%) as white solid: mp 205-207° C.; EI-HRMS m/e calcd for C15H14BrN3OS (M+) 363.0041, found 363.0034.

Workup

  1. stirringThe reaction was stirred at 0° C. for 15 min
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 15 min
  4. stirringstirred at 25° C. for 18 h
  5. customAt this time, the mixture was partitioned between water (150 mL) and ethyl acetate (150 mL)
  6. additiontreated with a 1N aqueous hydrochloric acid solution (100 mL)
  7. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×100 mL), water (1×100 mL)
  8. dry with materialThe organic layer was then dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-10d4bfd4b285456ca44b785404b52ff7
Source dataset
uspto-grants-2005_04
Patent number
US06881844B2

Reaction notes

Loading…