Hydrochloric Acid → HCID 72303266, compound

HRID 450826Notes

Reaction equation

HRID 450826 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][O:22][CH2:23][C:24]2[N:29]=[C:28]3[CH2:30][O:31]C(C)(C)[O:33][C:27]3=[CH:26][CH:25]=2)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:36])[N:10]1[CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]1[NH:43][S:44]([CH3:47])(=[O:46])=[O:45].Cl.C(=O)([O-])O.[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH:18]([C:19]([NH:21][O:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([OH:33])=[C:28]([CH2:30][OH:31])[N:29]=2)=[O:20])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:36])[N:10]1[CH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH:38]1[NH:43][S:44]([CH3:47])(=[O:45])=[O:46]

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 516892Sodium BicarbonateHCID 72303219HCID 72303219, compound

Product 1

HCID 72303266HCID 72303266, compoundYield 36.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 566 mg of (3RS,4RS)-3-(2,4-dichlorophenyl)-N-[(2,2-dimethyl-4H-[1,3]dioxino[5,4-b]pyridin-6-yl)methoxy]-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide in 11.3 ml of THF was added 3.2 ml of 1 M hydrochloric acid, followed by stirring at room temperature for 2 hours. 1.6 ml of 1 M hydrochloric acid was further added, followed by stirring for 2 days. The solution was neutralized with a saturated aqueous sodium hydrogen carbonate solution and then extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol) and recrystallized from ethyl acetate to obtain 196 mg of rel-(3RS,4RS)-3-(2,4-dichlorophenyl)-N-{[5-hydroxy-6-(hydroxymethyl)pyridin-2-yl]methoxy}-2-{(1SR,2SR)-2-[(methylsulfonyl)amino]cyclohexyl}-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxamide as a white crystal.

Workup

  1. stirringby stirring for 2 days
  2. extractionextracted with chloroform
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (eluent: chloroform-methanol)
  6. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-38857d3206604fa28f30d22bc415c3de
Source dataset
uspto-grants-2013_07
Patent number
US08486970B2

Reaction notes

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