Chloride → HCID 178482329, compound

HRID 1620247Notes

Reaction equation

HRID 1620247 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH3:15])=[N:8][C:7]([OH:16])=[C:6]2[CH2:17][C:18]1[C:19]([NH:31][CH3:32])=[N:20][C:21]2[CH:22]=[C:23]3[O:30]C[O:28][C:24]3=[CH:25][C:26]=2[CH:27]=1.B(Cl)(Cl)[Cl:34].[Cl-:37]>C(Cl)Cl>[ClH:34].[ClH:37].[OH:16][C:7]1[N:8]=[C:9]([CH3:15])[C:10]2[C:5]([C:6]=1[CH2:17][C:18]1[C:19]([NH:31][CH3:32])=[N:20][C:21]3[C:26]([CH:27]=1)=[CH:25][C:24]([OH:28])=[C:23]([OH:30])[CH:22]=3)=[CH:4][C:3]([O:2][CH3:1])=[C:12]([O:13][CH3:14])[CH:11]=2

Participants

5

Reactant 3

HCID 312ChlorideHCID 25135Boron TrichlorideHCID 178482302HCID 178482302, compound

Product 1

HCID 178482329HCID 178482329, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6,7-dimethoxy-1-methyl-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol 60 free base (28 mg, 65 μmol) in dry CH2Cl2 (5 mL) at 0° C. in a 25 mL round-bottomed flask equipped with a magnetic stirrer under N2 was added dropwise BCl3 (1.0 N solution in CH2Cl2, 0.30 mL, 0.30 mmol). After complete addition, the bath was immediately removed and stirring was continued overnight at RT. The reaction mixture was then carefully quenched with MeOH (3 mL) and the mixture was concentrated to dryness at 40° C. under vacuum before purification by prep. HPLC (eluent H2O:CH3CN:TFA=100:0:0.05 to 60:40:0.05 in 10 min) and lyophilisation. The residue was then dissolved in a 0.19 N HCl solution in MeOH (5 mL) before concentration at 40° C. under vacuum. Ion exchange on Amberlite IRA-400 (chloride form, 50 eq.) finally afforded 3-((3-hydroxy-6,7-dimethoxy-1-methylisoquinolin-4-yl)methyl)-2-(methylamino)quinoline-6,7-diol dihydrochloride 59 as a brown solid (10 mg, 31% yield).

Workup

  1. additionAfter complete addition
  2. customthe bath was immediately removed
  3. customThe reaction mixture was then carefully quenched with MeOH (3 mL)
  4. concentrationthe mixture was concentrated to dryness at 40° C. under vacuum before purification by prep
  5. customHPLC (eluent H2O:CH3CN:TFA=100:0:0.05 to 60:40:0.05 in 10 min) and lyophilisation
  6. dissolutionThe residue was then dissolved in a 0.19 N HCl solution in MeOH (5 mL) before concentration at 40° C. under vacuum

Sources & evidence

ORD record
ord-2c99f15691fd4bada7b2e4fc1cb49c2d
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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