Phosphorus oxychloride → Isoquinoline, 1-chloro-

HRID 629483Notes

Reaction equation

HRID 629483 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-5520825b52e94164a114202071c75ae8
Source dataset
uspto-grants-2016_04
Patent number
US09315505B2

Reaction notes

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