Hydrochloric Acid → HCID 15606384, compound

HRID 2217086Notes

Reaction equation

HRID 2217086 reaction equation
CC(C)([O-])C.[K+].[CH2:7]([NH:10][N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1)[CH2:8][CH3:9].[Cl:20][C:21]1[CH:26]=[CH:25][N:24]=[CH:23][C:22]=1[F:27].Cl>CN1C(=O)CCC1.CCCCCCC.O>[ClH:20].[F:27][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][C:21]=1[N:10]([N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1)[CH2:7][CH2:8][CH3:9]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 38524294-Chloro-3-fluoropyridineHCID 107023901H-Indol-1-amine, N-propyl-HCID 23665647Potassium tert-butoxide

Product 1

HCID 15606384HCID 15606384, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8900HeptaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
20 °C

Procedure

Prepare a solution of 18.0 g potassium tert-butoxide in 53 mL NMP and stir the suspension at 20° C. until a clear solution is obtained. Cool the solution to −20° C. Add to the cooled solution a mixture of 9.3 g (53.4 mmol) N-propyl-1H-indol-1-amine, 7.4 g (53.4 mmol) 4-chloro-3-fluoropyridine and 53 mL NMP while maintaining the internal reaction temperature around −15° C. After the addition is over, the reaction mixture is stirred for ˜30 min at −20° C. The reaction mixture is then added to 100 mL water and 13 mL HCl (37%). Then, add 50 mL n-heptane (2×) and separate the phases. Add to the water phase 10 mL NaOH (32%) and extract the water phase twice with 50 mL n-butyl acetate, wash the combined n-butyl acetate phase with 50 mL water. Add to the resulting n-butyl acetate phase 4.5 mL HCl (37%). Distill the mixture using Dean-Stark trap to remove completely the water. During the distillation a solid precipitates. The suspension is cooled to 5° C. and filtered. After drying at 60–70° C., there remains 10.8 g (3-fluoro-pyridin-4-yl)-(indol-1-yl)-propylamine hydrochloride (75%) as a slightly yellow solid.

Workup

  1. customis obtained
  2. temperatureCool the solution to −20° C
  3. additionAdd to the cooled solution
  4. temperaturewhile maintaining the internal reaction temperature around −15° C
  5. additionAfter the addition
  6. stirringis stirred for ˜30 min at −20° C
  7. customseparate the phases
  8. additionAdd to the water phase 10 mL NaOH (32%)
  9. extractionextract the water phase twice with 50 mL n-butyl acetate
  10. washwash the combined n-butyl acetate phase with 50 mL water
  11. additionAdd to the resulting n-butyl acetate phase 4.5 mL HCl (37%)
  12. distillationDistill the mixture
  13. customto remove completely the water
  14. distillationDuring the distillation a solid
  15. customprecipitates
  16. temperatureThe suspension is cooled to 5° C.
  17. filtrationfiltered
  18. customAfter drying at 60–70° C.

Sources & evidence

ORD record
ord-8b5793dfe84d4cacac705ce125f27053
Source dataset
uspto-grants-2006_09
Patent number
US07112682B2

Reaction notes

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