Hydrochloric Acid → HCID 70976636, compound

HRID 882240Notes

Reaction equation

HRID 882240 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([C:20](=[O:27])[NH:21][CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:28]C(=O)OC(C)(C)C)[CH2:6][C@@H:5]1[CH3:36])(=[O:3])[CH3:2].F[P-](F)(F)(F)(F)F.Cl>O1CCOCC1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([NH:21][CH2:22][CH2:23][N:24]([CH3:25])[CH3:26])=[O:27])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:28])[CH2:6][C@@H:5]1[CH3:36])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 9886HexafluorophosphateHCID 86709415HCID 86709415, compound

Product 1

HCID 70976636HCID 70976636, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A suspension of crushed tert-butyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (for a preparation see Intermediate 41) (8 g, possibly as the PF6 salt) was treated with 1,4-dioxane (30 mL) followed by hydrogen chloride in 1,4-dioxane (4N, 40 mL, 160 mmol). After −30 min most of the dioxane was removed and the residue dissolved in warm MeOH (100 mL) at 70° C. for 1.5 h. The residual insoluble material which was filtered off and discarded. The filtrate was concentrated in vacuo and purified using a SCX column (70 G, pre-conditioned with MeOH.) The cartridge was washed with MeOH (200 ml) and eluted with ammonia in MeOH (2M, 200 ml). The methanolic ammonia fractions were combined and concentrated in vacuo to give 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-(dimethylamino)ethyl)benzamide (3.65 g, 9.25 mmol, 84% yield) as a yellow foam. LCMS (HpH, 2 min), Rt=0.71 min, MH+=395.

Workup

  1. customAfter −30 min most of the dioxane was removed
  2. dissolutionthe residue dissolved in warm MeOH (100 mL) at 70° C. for 1.5 h
  3. filtrationThe residual insoluble material which was filtered off
  4. concentrationThe filtrate was concentrated in vacuo
  5. custompurified
  6. washwas washed with MeOH (200 ml)
  7. washeluted with ammonia in MeOH (2M, 200 ml)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-624088dcffe147068b86362653a676dc
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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