Pyridine → HCID 11292392, compound

HRID 1833275Notes

Reaction equation

HRID 1833275 reaction equation
[N+:1]([C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[C:7]([C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=2)=[O:19])=[N:6][CH:5]=1)([O-])=O.[Sn](Cl)(Cl)(Cl)Cl.N1C=CC=CC=1.[CH3:39][O:40][C:41](Cl)=[O:42]>C1COCC1.Cl>[CH3:39][O:40][C:41](=[O:42])[NH:1][C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[C:7]([C:18](=[O:19])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=2)=[N:6][CH:5]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6586Methyl chloroformateHCID 24287Tin tetrachlorideHCID 22048297HCID 22048297, compound

Product 1

HCID 11292392HCID 11292392, compoundYield 23.9%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

The above [4-nitro-6,7-dimethoxy-isoquinolin-1-yl]-(3-methoxy-phenyl)-methanone (150 mg, 0.407 mmol) was treated with tin chloride (459 mg, 2.03 mmol) in THF (30 mL) and 6N HCl (19 mL) at room temperature overnight. The reaction mixture was treated with ice-cold saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and dried to a crude solid. 75 mg (0.203 mmol) of this crude solid was dissolved in dry THF (5 mL) and treated with pyridine (24.6 uL, 0.364 mmol) and methylchloroformate (18.7 uL, 0.243 mmol) under argon at 0° C. The reaction was stirred at room temperature overnight. The reaction mixture was poured into ice water and extracted with ethyl acetate. The combined ethyl acetate layers were dried over magnesium sulfate, filtered, and evaporated to crude product. Preparative HPLC purification yielded 23 mg of [6,7-dimethoxy-1-(3-methoxy-benzoyl)-isoquinolin-4-yl]-carbamic acid methyl ester; trifluoro-acetic acid salt as an off-white solid: APCI-MS (M+H+) m/e calcd for C21H20N2O6 397.4, found 397.4; 1H NMR (300 MHz) compatible.

Workup

  1. additionThe reaction mixture was treated with ice-cold saturated sodium bicarbonate
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. customdried to a crude solid
  6. extractionextracted with ethyl acetate
  7. dry with materialThe combined ethyl acetate layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated to crude product
  10. customPreparative HPLC purification

Sources & evidence

ORD record
ord-d0dcf999046547979355772371f481e0
Source dataset
uspto-grants-2006_06
Patent number
US07067529B2

Reaction notes

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