Hydrochloric Acid → 6,7-Dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 1892614Notes

Reaction equation

HRID 1892614 reaction equation
C(OC(N1CCC2C(=CC(OC)=C(OC)C=2)C1CC1C=CC(Br)=CC=1)=O)(C)(C)C.COC1C(B(O)O)=CC=CN=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+].[C:66]([O:70][C:71]([N:73]1[CH2:82][CH2:81][C:80]2[C:75](=[CH:76][C:77]([O:85][CH3:86])=[C:78]([O:83][CH3:84])[CH:79]=2)[CH:74]1[CH2:87][C:88]1[CH:93]=[CH:92][C:91]([C:94]2[C:95]([O:100][CH3:101])=[N:96][CH:97]=[CH:98][CH:99]=2)=[CH:90][CH:89]=1)=[O:72])([CH3:69])([CH3:68])[CH3:67].[ClH:102]>C(O)(C)C.C(OCC)C>[C:66]([O:70][C:71]([N:73]1[CH2:82][CH2:81][C:80]2[C:75](=[CH:76][C:77]([O:85][CH3:86])=[C:78]([O:83][CH3:84])[CH:79]=2)[CH:74]1[CH2:87][C:88]1[CH:89]=[CH:90][C:91]([C:94]2[C:95]([O:100][CH3:101])=[N:96][CH:97]=[CH:98][CH:99]=2)=[CH:92][CH:93]=1)=[O:72])([CH3:68])([CH3:69])[CH3:67].[ClH:102].[CH3:84][O:83][C:78]1[CH:79]=[C:80]2[C:75](=[CH:76][C:77]=1[O:85][CH3:86])[CH:74]([CH2:87][C:88]1[CH:89]=[CH:90][C:91]([C:94]3[C:95]([O:100][CH3:101])=[N:96][CH:97]=[CH:98][CH:99]=3)=[CH:92][CH:93]=1)[NH:73][CH2:82][CH2:81]2

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 589064711-(4-Bromo-benzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterHCID 597442806,7-Dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Product 2

HCID 597442806,7-Dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterHCID 690673856,7-Dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride salt

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 3776IsopropanolSolvent

Procedure

6,7-Dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 6 was synthesized by the Suzuki coupling of 1-(4-bromobenzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 1 with 2-methoxypyridine-3-boronic acid 5 using Palladium(II) acetate, triphenylphosphine, and Na2CO3 in anhydrous isopropanol. Compound 6 was treated with 2 M HCl solution in diethylether to get 6,7-dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride salt 7. Reaction of 7 with formaldehyde in the presence of sodium cyanoborohydride, and zinc chloride furnished 6,7-dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-2-methyl-1,2,3,4-tetrahydro-isoquinoline 8 which was treated with 2 M HCl solution in diethylether to obtain 6,7-dimethoxy-1-[4-(2-methoxypyridin-3-yl)benzyl]-2-methyl-1,2,3,4-tetrahydro-isoquinolinehydrochloride 9 (Scheme-2).

Sources & evidence

ORD record
ord-108647c82e9249a3a4113598c39bd170
Source dataset
uspto-grants-2013_08
Patent number
US08507523B2

Reaction notes

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