Water → HCID 178486673, compound

HRID 1620158Notes

Reaction equation

HRID 1620158 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][C:9]2[C:18]3[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=3)[C:12]([CH3:23])=[N:11][C:10]=2[OH:24])[CH:5]=[N:6][CH:7]=1.[C:25]1(B(O)O)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+].O>CCO.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(COC)OC>[CH3:20][O:19][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][C:15]=1[O:21][CH3:22])[C:12]([CH3:23])=[N:11][C:10]([OH:24])=[C:9]2[CH2:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:3]=1

Participants

9

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 178486672HCID 178486672, compound2×

Product 1

HCID 178486673HCID 178486673, compound

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 4-((5-bromopyridin-3-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 34166 (66 mg, 170 μmol) in absolute EtOH (0.9 mL) in a 20 mL microwave vial equipped with a magnetic stirrer were added phenylboronic acid (20 mg, 164 μmol), Pd(PPh3)2Cl2 (10 mg, 14 μmol), a 2 N aq. Na2CO3 solution (0.30 mL, 0.60 mmol), H2O (2.7 mL) and dimethoxyethane (3.5 mL) and the resulting mixture was stirred at 140° C. for 25 min. After cooling to RT, the mixture was diluted with EtOAc (30 mL) and the solution was filtered through a celite plug, then washed with brine (10 mL). The organic layer was isolated and the celite plug was then further washed with CH2Cl2 (50 mL) and the organic layer was washed with brine (20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 92:8) provided 60 mg of 6,7-dimethoxy-1-methyl-4-((5-phenylpyridin-3-yl)methyl)isoquinolin-3-ol. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (1.0 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to give 6,7-dimethoxy-1-methyl-4-((5-phenylpyridin-3-yl)methyl)isoquinolin-3-ol dihydrochloride 15 as a pale brown solid (71 mg, 91% yield).

Workup

  1. filtrationthe solution was filtered through a celite plug
  2. washwashed with brine (10 mL)
  3. customThe organic layer was isolated
  4. washthe celite plug was then further washed with CH2Cl2 (50 mL)
  5. washthe organic layer was washed with brine (20 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated at 40° C. under vacuum
  9. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 92:8)

Sources & evidence

ORD record
ord-e2900f99d2d44697b1f8c3cf5f3b77f0
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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