Methyl 8-[bis-(tert-butoxycarbonyl)amino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate → Methyl 8-[bis-(tert-butoxycarbonyl)amino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate

HRID 595118Notes

Reaction equation

HRID 595118 reaction equation
[C:1]([O:5][C:6]([N:8]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:9]1[CH:18]=[CH:17][C:16]2[C:15]3=[CH:19][CH:20]=[N:21][N:14]3[CH:13]=[CH:12][C:11]=2[C:10]=1[C:22]([O:24][CH3:25])=[O:23])=[O:7])([CH3:4])([CH3:3])[CH3:2]>O1CCOCC1.[OH-].[OH-].[Pd+2]>[C:29]([O:28][C:26]([N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C:9]1[CH:18]=[CH:17][C:16]2[C:15]3=[CH:19][CH:20]=[N:21][N:14]3[CH2:13][CH2:12][C:11]=2[C:10]=1[C:22]([O:24][CH3:25])=[O:23])=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

4

Reactant 1

HCID 70984535Methyl 8-[bis-(tert-butoxycarbonyl)amino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate2×

Product 1

HCID 70984636Methyl 8-[bis-(tert-butoxycarbonyl)amino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylateYield 12.2%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl 8-[bis-(tert-butoxycarbonyl)amino]-pyrazolo[5,1-a]isoquinoline-7-carboxylate (Intermediate 7, 0.36 g) in dioxane was passed through the H-Cube, using a 20% palladium hydroxide on carbon cartridge, eluting at 0.5 mL/minute, at 100° C. and 100 bar. Two fractions were isolated. The first fraction was concentrated in vacuo to give methyl 8-[bis-(tert-butoxycarbonyl)amino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (0.044 g). The second fraction, containing the starting material was concentrated in vacuo then dissolved in a mixture of acetic acid in dioxane solution (20%, 40 mL) and was passed through the H-Cube®, using a 20% palladium hydroxide on carbon cartridge, eluting at 1 mL/minute, at 95° C. and 100 bar. The eluent was concentrated in vacuo and the residue purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-80% to give a solid which was combined with the earlier product to give a 3:7 mixture of methyl 8-[bis-(tert-butoxycarbonyl)amino]-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate and methyl 8-tert-butoxycarbonylamino-5,6-dihydropyrazolo[5,1-a]isoquinoline-7-carboxylate (0.084 g).

Workup

  1. washeluting at 0.5 mL/minute, at 100° C.
  2. customTwo fractions were isolated
  3. concentrationThe first fraction was concentrated in vacuo

Sources & evidence

ORD record
ord-92a770b451e04d6783b545061036ef5a
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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