Hydrochloric Acid → HCID 131735121, compound

HRID 2207721Notes

Reaction equation

HRID 2207721 reaction equation
C([NH:4][CH2:5][C@H:6]([C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[CH:15][CH:14]=[C:13]2[C:18]([NH:20][CH3:21])=[O:19])[CH3:7])(=O)C.[ClH:22].[OH-].[Na+].Cl.CC(O)C.Cl.NC[C@H](C1C=CC=C2C=1N=CC=C2C(NC)=O)C>CCOC(C)=O>[ClH:22].[ClH:22].[NH2:4][CH2:5][C@H:6]([C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:17]=1[N:16]=[CH:15][CH:14]=[C:13]2[C:18]([NH:20][CH3:21])=[O:19])[CH3:7]

Participants

7

Reactant 5

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 21912024Isopropanol hydrochlorideHCID 86699666HCID 86699666, compound2×HCID 131735122HCID 131735122, compound

Product 1

HCID 131735121HCID 131735121, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

As shown in step 10-iii of Scheme 10, (S)-8-(1-acetamidopropan-2-yl)-N-methylquinoline-4-carboxamide (11.0 g, 38.55 mmol) in 6M aqueous HCl (192.7 mL, 1.156 mol) was warmed to 60° C. After stirring for 2 days at this temperature, the reaction mixture was cooled and an additional 20 mL of 6M HCl was added. Stirring was continued for an additional 2 days at 70° C. The reaction mixture was cooled with an ice bath and the pH adjusted to about 11 with 6M NaOH (aq). The aqueous mixture was extracted with 5% MeOH/DCM and the combined organic extracts washed with water (60 mL), brine (100 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford crude product as a tan solid. This solid was suspended in EtOAc (200 mL), cooled to 3° C. with an ice bath, and 6M HCl/i-PrOH (30 mL) was added portionwise to produce a white precipitate which was collected by filtration. The solid was washed with EtOAc (100 mL) and dried under high vacuum to provide (S)-8-(1-aminopropan-2-yl)-N-methylquinoline-4-carboxamide, dihydrochloride [compound 2038, 7.8 g, 61% yield, 95% purity (5% compound 2041)] as a white solid. This material was used as is in subsequent reactions.

Workup

  1. temperaturethe reaction mixture was cooled
  2. stirringStirring
  3. waitwas continued for an additional 2 days at 70° C
  4. temperatureThe reaction mixture was cooled with an ice bath
  5. extractionThe aqueous mixture was extracted with 5% MeOH/DCM
  6. washthe combined organic extracts washed with water (60 mL), brine (100 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford crude product as a tan solid
  11. temperaturecooled to 3° C. with an ice bath
  12. customto produce a white precipitate which
  13. filtrationwas collected by filtration
  14. washThe solid was washed with EtOAc (100 mL)
  15. customdried under high vacuum

Sources & evidence

ORD record
ord-afb1df2809974ba6923c2afd3246b393
Source dataset
uspto-grants-2016_06
Patent number
US09376448B2

Reaction notes

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