Water → HCID 178437785, compound

HRID 1620152Notes

Reaction equation

HRID 1620152 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9]([CH2:20][CH3:21])=[N:8][C:7]=1[OH:22].[NH2:26][C:27]1[CH:28]=[C:29](B(OC(C)(C)C)OC(C)(C)C)[CH:30]=[CH:31][CH:32]=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>[NH2:26][C:27]1[CH:32]=[C:31]([C:2]2[CH:25]=[CH:24][CH:23]=[C:4]([CH2:5][C:6]3[C:15]4[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=4)[C:9]([CH2:20][CH3:21])=[N:8][C:7]=3[OH:22])[CH:3]=2)[CH:30]=[CH:29][CH:28]=1

Participants

9

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 68182169HCID 68182169, compoundHCID 178437783HCID 178437783, compound2×

Product 1

HCID 178437785HCID 178437785, compound

Reagents, catalysts & solvents 4

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

Procedure

To a stirred solution of 4-(3-bromobenzyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28138 (79 mg, 0.196 mmol) in EtOH (0.9 mL) in a 20 mL microwave vial equipped with a magnetic stirrer were added di-tert-butyl 3-aminophenylboronate (49 mg, 0.393 mmol), Pd(PPh3)2Cl2 (10.0 mg), a 2 N aq. Na2CO3 solution (0.3 mL), 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 organic solution was passed through a celite plug, then washed with brine (10 mL). 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 98:2) gave 4-((3′-amino-[1,1′-biphenyl]-3-yl)methyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol. This free base was dissolved in CH2Cl2 (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 (3 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 4-((3′-amino-[1,1-biphenyl]-3-yl)methyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 10 as a yellow solid (43 mg, 69% yield).

Workup

  1. washwashed with brine (10 mL)
  2. washThe celite plug was then further washed with CH2Cl2 (50 mL)
  3. washthe organic layer was washed with brine (20 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated at 40° C. under vacuum
  7. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 98:2)

Sources & evidence

ORD record
ord-d81c4581c0b74ad5921da856ebc876e8
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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