Formic Acid → N-Methyl-2-(1,3-thiazol-2-yl)-1H-indole-7-amine hydrochloride

HRID 1851398Notes

Reaction equation

HRID 1851398 reaction equation
C(O)=O.[C:4](OC(=O)C)(=O)C.[S:11]1[CH:15]=[CH:14][N:13]=[C:12]1[C:16]1[NH:17][C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[CH:20][C:19]=2[NH2:25].C(OCC)(=O)C.[ClH:32]>O1CCCC1>[ClH:32].[CH3:4][NH:25][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]2[C:18]=1[NH:17][C:16]([C:12]1[S:11][CH:15]=[CH:14][N:13]=1)=[CH:24]2

Participants

6

Reactant 4

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 21866389Hydrogen chloride-ethyl acetateHCID 579018012-(1,3-Thiazol-2-yl)-1H-indole-7-amine

Product 1

HCID 67109280N-Methyl-2-(1,3-thiazol-2-yl)-1H-indole-7-amine hydrochlorideYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Under ice-cooling, formic acid (6.0 mL) was added dropwise to acetic anhydride (12.5 mL). After dropwise addition, the reaction mixture was stirred at 60° C. for 2 hr. Tetrahydrofuran (10 mL) was added to the reaction mixture, and a solution of 2-(1,3-thiazol-2-yl)-1H-indole-7-amine (10 g) in tetrahydrofuran (10 mL) was added dropwise under ice-cooling. The reaction mixture was stirred for 30 min and concentrated. Tetrahydrofuran (10 mL) was added to the obtained residue, and borane-tetrahydrofuran complex (1.0 M tetrahydrofuran solution, 30 mL) was added. The reaction mixture was stirred with heating under reflux for 1 hr. The reaction mixture was cooled to room temperature, and methanol (5 mL) was added. The reaction mixture was stirred with heating under reflux for 1 hr, concentrated, and the obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1). To the obtained a yellow oil was added 4N hydrogen chloride-ethyl acetate solution (30 mL). The obtained yellow crystals were collected by filtration, and washed with diethyl ether and hexane to give the title compound (10 g, yield 70%) as yellow crystals. melting point 89° C.

Workup

  1. temperatureUnder ice-cooling
  2. additionAfter dropwise addition
  3. temperaturecooling
  4. stirringThe reaction mixture was stirred for 30 min
  5. concentrationconcentrated
  6. additionTetrahydrofuran (10 mL) was added to the obtained residue, and borane-tetrahydrofuran complex (1.0 M tetrahydrofuran solution, 30 mL)
  7. additionwas added
  8. stirringThe reaction mixture was stirred
  9. temperaturewith heating
  10. temperatureunder reflux for 1 hr
  11. temperatureThe reaction mixture was cooled to room temperature
  12. additionmethanol (5 mL) was added
  13. stirringThe reaction mixture was stirred
  14. temperaturewith heating
  15. temperatureunder reflux for 1 hr
  16. concentrationconcentrated
  17. customTo the obtained a yellow oil
  18. filtrationThe obtained yellow crystals were collected by filtration
  19. washwashed with diethyl ether and hexane

Sources & evidence

ORD record
ord-7ee1040d1b6c4e11b9666a2678527309
Source dataset
uspto-grants-2015_02
Patent number
US08957070B2

Reaction notes

Loading…