2-Aminothiazole → HCID 10471824, compound

HRID 1816097Notes

Reaction equation

HRID 1816097 reaction equation
[CH:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([N+:13]([O-:15])=[O:14])[CH:11]=2)[C:6]([C:16]([OH:18])=O)=[CH:5]1)([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:55][C:56]1[S:57][CH:58]=[CH:59][N:60]=1>C(Cl)Cl>[S:57]1[CH:58]=[CH:59][N:60]=[C:56]1[NH:55][C:16]([C:6]1[C:7]2[C:12](=[CH:11][C:10]([N+:13]([O-:15])=[O:14])=[CH:9][CH:8]=2)[N:4]([CH:1]([CH3:2])[CH3:3])[CH:5]=1)=[O:18]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 22497217HCID 22497217, compound

Product 1

HCID 10471824HCID 10471824, compoundYield 4.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 1-isopropyl-6-nitro-1H-indole-3-carboxylic acid (200 mg, 0.81 mmol) in methylene chloride (4 mL) and N,N-diisopropylethylamine (0.32 mL, 1.85 mmol) at 25° C. was treated with benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluoro-phosphate (463 mg, 1.05 mmol). The reaction was stirred at 25° C. for 20 min. At this time, the reaction was treated with 2-aminothiazole (186 mg, 1.85 mmol) and was stirred at 25° C. for 24 h. At this time, the reaction mixture was partitioned between water (50 mL) and ethyl acetate (50 mL) and was treated with a 1N aqueous hydrochloric acid solution (25 mL). The organic layer was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dissolved in a hot solution of 1/1 hexanes/ethyl acetate and then filtered. The filtrate was cooled in the freezer for 1 h. At this time, the resulting solid was collected by filtration. The filtrate was concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 1-isopropyl-6-nitro-1H-indole-3-carboxylic acid thiazol-2-ylamide (13 mg, 4.9%) as a yellow solid: mp 236-239° C.; EI-HRMS m/e calcd for C15H14N4O3S (M+) 330.0786, found 330.0792.

Workup

  1. stirringwas stirred at 25° C. for 24 h
  2. customAt this time, the reaction mixture was partitioned between water (50 mL) and ethyl acetate (50 mL)
  3. additionwas treated with a 1N aqueous hydrochloric acid solution (25 mL)
  4. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe resulting solid was dissolved in a hot solution of 1/1 hexanes/ethyl acetate
  9. filtrationfiltered
  10. temperatureThe filtrate was cooled in the freezer for 1 h
  11. filtrationAt this time, the resulting solid was collected by filtration
  12. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-c80aac4bf3a246f2b18ac6dbd643de19
Source dataset
uspto-grants-2005_04
Patent number
US06881844B2

Reaction notes

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