2-Aminothiazole → HCID 10066302, compound

HRID 1816131Notes

Reaction equation

HRID 1816131 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([C:43]([OH:45])=O)=[CH:34][N:35]2[CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[CH:31][CH:30]=1.[NH2:46][C:47]1[S:48][CH:49]=[CH:50][N:51]=1>C(Cl)Cl>[S:48]1[CH:49]=[CH:50][N:51]=[C:47]1[NH:46][C:43]([C:33]1[C:32]2[C:36](=[CH:37][C:29]([Cl:28])=[CH:30][CH:31]=2)[N:35]([CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[CH:34]=1)=[O:45]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 22497215HCID 22497215, compound

Product 1

HCID 10066302HCID 10066302, compoundYield 25.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (355 mg, 1.35 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (240 mg, 1.35 mmol). The reaction was stirred at 0° C. for 15 min. At this time, the reaction was treated with 6-chloro-1-pentyl-1H-indole-3-carboxylic acid (300 mg, 1.13 mmol). The reaction was stirred at 0° C. for 10 min and then was allowed to warm to 25° C. where it was stirred for 1 h. The reaction was then treated with 2-aminothiazole (283 mg, 2.83 mmol) and stirred at 25° C. for 3 d. At this time, the reaction was partitioned between water (50 mL) and ethyl acetate (50 mL). This mixture was treated with a 10% aqueous hydrochloric acid solution (15 mL), shaken, and separated. 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. Biotage chromatography (FLASH 40S, Silica, 2/1 hexanes/ethyl acetate) afforded 6-chloro-1-pentyl-1H-indole-3-carboxylic acid thiazol-2-ylamide (101 mg, 25%) as a pink solid: mp 139-141° C.; EI-HRMS m/e calcd for C17H18ClN3OS (M+) 347.0859, found 347.0859.

Workup

  1. stirringThe reaction was stirred at 0° C. for 10 min
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 1 h
  4. stirringstirred at 25° C. for 3 d
  5. customAt this time, the reaction was partitioned between water (50 mL) and ethyl acetate (50 mL)
  6. additionThis mixture was treated with a 10% aqueous hydrochloric acid solution (15 mL)
  7. stirringshaken
  8. customseparated
  9. washThe organic layer was washed with a saturated aqueous sodium bicarbonate solution (1×30 mL), water (1×30 mL)
  10. dry with materialThe organic layer was then dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e48d63161378415eab8d5eddfd57b333
Source dataset
uspto-grants-2005_04
Patent number
US06881844B2

Reaction notes

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