Phosphorus oxychloride → Isoquinoline, 1-chloro-

HRID 1626322Notes

Reaction equation

HRID 1626322 reaction equation
C(O[C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][N:6]=1)(C)C.P(Cl)(Cl)([Cl:17])=O>C(#N)C>[Cl:17][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][N:6]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 20743620HCID 20743620, compound

Product 1

HCID 140539Isoquinoline, 1-chloro-

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Methyl ester 104 is coupled with compound 7, which is synthesized as described in Reaction Scheme 1, in the presence of palladium acetate coupling catalyst, tetrabutylammonium fluoride, sodium bicarbonate in dimethyl formamide at 100° C., to produce compound 105. Compound 105 is converted to isopropoxy isoquinoline compound 107 by one of two methods. In the first method, compound 105 is treated with phosphoryl chloride in refluxing acetonitrile to produce the 1-chloro isoquinoline compound 106, which is then reacted with isopropyl alcohol in the presence of sodium hydride base to product compound 107. Alternatively, compound 105 is converted directly to compound 107 by reaction with isopropyl bromide, in dimethylformamide at 80° C., in the presence of potassium tert-butoxide.

Sources & evidence

ORD record
ord-23fc11f7f4fc42398a64f100edc88d47
Source dataset
uspto-grants-2014_07
Patent number
US08785454B2

Reaction notes

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