Formaldehyde → HCID 59744272, compound

HRID 1892617Notes

Reaction equation

HRID 1892617 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH:10]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][C:28]=3[O:29][CH3:30])=[CH:19][CH:18]=1)[NH:9][CH2:8][CH2:7]2.C=O.[C:33]([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[CH:10]([CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][C:28]=3[O:29][CH3:30])=[CH:21][CH:22]=1)[N:9]([CH3:33])[CH2:8][CH2:7]2

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 69069609HCID 69069609, compound

Product 1

HCID 59744272HCID 59744272, compound

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

The synthesis of 6,7-dimethoxy-1-[4-(4-methoxypyridin-3-yl)benzyl]-2-methyl-1,2,3,4-tetrahydroisoquinoline hydrochloride 23 is shown in Scheme 6. 6,7-Dimethoxy-1-[4-(4-methoxypyridin-3-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 20 was prepared by the reaction of 1-(4-bromobenzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 1 with 4-methoxypyridine-3-boronic acid 19 in the presence of Palladium(II) acetate, triphenylphosphine, and Na2CO3 in anhydrous isopropanol. Reaction of compound 20 with 2 M HCl solution in diethylether gave 6,7-dimethoxy-1-[4-(4-methoxypyridin-3-yl)benzyl]-1,2,3,4-tetrahydroisoquinolinehydrochloride salt 21. Reaction of 21 with formaldehyde, sodium cyanoborohydride, and zinc chloride in methanol furnished 6,7-dimethoxy-1-[4-(4-methoxypyridin-3-yl)benzyl]-2-methyl-1,2,3,4-tetrahydroisoquinoline 22 which was then reacted with 2 M HCl solution in diethylether to yield the compound 23.

Sources & evidence

ORD record
ord-1317ab2dd28a4d9a97a141fbf19a1bdb
Source dataset
uspto-grants-2013_08
Patent number
US08507523B2

Reaction notes

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