Pyridine → HCID 67271083, compound

HRID 1696552Notes

Reaction equation

HRID 1696552 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[NH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(C1C=C(C(OCC)=O)NN=1)(C)(C)C.[C:34]([O:38][C:39]([N:41]1[CH:50]([C:51]([O:53][CH3:54])=[O:52])[CH2:49][C:48]2[C:43](=[CH:44][CH:45]=[C:46](B(O)O)[CH:47]=2)[CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH2:13]([O:12][C:10]([C:8]1[N:7]([C:46]2[CH:47]=[C:48]3[C:43](=[CH:44][CH:45]=2)[CH2:42][N:41]([C:39]([O:38][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:40])[CH:50]([C:51]([O:53][CH3:54])=[O:52])[CH2:49]3)[N:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:9]=1)=[O:11])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 2743509Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylateHCID 57355547[2-(tert-Butoxycarbonyl)-3-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]boronic acidHCID 178441086HCID 178441086, compound

Product 1

HCID 67271083HCID 67271083, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl 3-t-butyl-1H-pyrazole-5-carboxylate (0.100 g, 0.387 mmol, synthesized by trans-esterification of commercially available ethyl 3-t-butyl-1H-pyrazole-5-carboxylate), 2-(t-butoxycarbonyl)-3-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-ylboronic acid (0.195 g, 0.581 mmol, made analogously to Example A56) and pyridine (0.092 g, 1.16 mmol) in methylene chloride (4 mL) was added copper(II)-acetate (0.105 g, 0.581 mmol) and the resulting mixture was stirred at Rt for 1d. The mixture was directly loaded on a silica gel column, chromatographed and concentrated to yield 2-t-butyl 3-methyl 6-(5-(benzyloxycarbonyl)-3-t-butyl-1H-pyrazol-1-yl)-3,4-dihydroisoquinoline-2,3 (1H)-dicarboxylate (171 mg, 81% yield) as a colorless foam. MS expected 548.3 found 548.3. To this material (0.136 g, 0.248 mmol) in EtOAc (5 mL) was added palladium on charcoal (10%, 0.013 g, 0.012 mmol) and the mixture was stirred under an atmosphere of H2 overnight. The mixture was filtered and the filtrate was concentrated to yield 1-(2-(t-butoxycarbonyl)-3-(methoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-3-t-butyl-1H-pyrazole-5-carboxylic acid (114 mg, 100%) as a colorless foam. MS expected 458.2 found 458.3.

Workup

  1. customchromatographed
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-4bce18a177b243a38c1d414a0ecafa5b
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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