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

HRID 1892615Notes

Reaction equation

HRID 1892615 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:28]=[CH:27][N:26]=[CH:25][C:24]=3[O:29][CH3:30])=[CH:19][CH:18]=1)[NH:9][CH2:8][CH2:7]2.[C:31]([O:35][C:36](N1CCC2C(=CC(OC)=C(OC)C=2)C1CC1C=CC(Br)=CC=1)=[O:37])([CH3:34])([CH3:33])[CH3:32].COC1C=NC=CC=1B(O)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:31]([O:35][C:36]([N:9]1[CH2:8][CH2:7][C:6]2[C:11](=[CH:12][C:13]([O:14][CH3:15])=[C:4]([O:3][CH3:2])[CH:5]=2)[CH:10]1[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][C:24]=2[O:29][CH3:30])=[CH:21][CH:22]=1)=[O:37])([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 467390193-Methoxypyridine-4-boronic acidHCID 589064711-(4-Bromo-benzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterHCID 690107786,7-Dimethoxy-1-[4-(3-methoxypyridin-4-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride salt

Product 1

HCID 597442816,7-dimethoxy-1-[4-(3-methoxypyridin-4-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

The synthesis of 6,7-dimethoxy-1-[4-(3-methoxypyridin-4-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride salt 12 is shown in Scheme 3. Reaction of 1-(4-bromobenzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 1 with 3-methoxypyridine-4-boronic acid 10 in the presence of Palladium(II) acetate, triphenylphosphine, and Na2CO3 yielded 6,7-dimethoxy-1-[4-(3-methoxypyridin-4-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 11 which was then treated with 2 M HCl solution in diethylether to get compound 12. N-[4′-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-ylmethyl)biphenyl-2-yl]-methanesulfonamide hydrochloride salt 15 was prepared by the reaction of 1-(2′-Methanesulfonyl-aminobiphenyl-4-ylmethyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 14 with 2 M HCl solution in diethylether. Compound 14 was obtained by the Suzuki coupling of compound 1 with (2-methylsulfonylaminophenyl)-boronic acid 13 using Palladium(II) acetate, triphenylphosphine, and Na2CO3 in isopropanol (scheme-4).

Sources & evidence

ORD record
ord-b0187737045c4cd6a4667b645f3c6620
Source dataset
uspto-grants-2013_08
Patent number
US08507523B2

Reaction notes

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