3-Methoxypropyne → 5-(4-Methoxymethyl-[1,2,3]triazol-1-yl)-6-(piperidin-4-yloxy)-isoquinoline

HRID 1022872Notes

Reaction equation

HRID 1022872 reaction equation
O=[C:2]1[O:8][C@H:7]([C@H](CO)O)[C:5]([O-])=[C:3]1O.[Na+].C(OC([N:21]1[CH2:26][CH2:25][CH:24]([O:27][C:28]2[C:29]([N:38]=[N+:39]=[N-:40])=[C:30]3[C:35](=[CH:36][CH:37]=2)[CH:34]=[N:33][CH:32]=[CH:31]3)[CH2:23][CH2:22]1)=O)(C)(C)C.C(OC)C#C.FC(F)(F)C([O-])=O>CCCCCCC.C(OCC)(=O)C.O.S([O-])([O-])(=O)=O.[Cu+2].C(OCC)(=O)C>[CH3:2][O:8][CH2:7][C:5]1[N:40]=[N:39][N:38]([C:29]2[C:28]([O:27][CH:24]3[CH2:23][CH2:22][NH:21][CH2:26][CH2:25]3)=[CH:37][CH:36]=[C:35]3[C:30]=2[CH:31]=[CH:32][N:33]=[CH:34]3)[CH:3]=1

Participants

8

Reactant 4

HCID 693933-MethoxypropyneHCID 84468TrifluoroacetateHCID 23667548Sodium AscorbateHCID 576467494-(5-Azido-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester

Product 1

HCID 576469685-(4-Methoxymethyl-[1,2,3]triazol-1-yl)-6-(piperidin-4-yloxy)-isoquinolineYield 40.9%

Reagents, catalysts & solvents 3

HCID 61499Cupric sulfate monohydrateCatalystHCID 8857Ethyl AcetateSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

4 mg (0.1 eq.) of sodium ascorbate and 0.5 mg (0.01 eq.) of Copper(II)sulfate-hydrate were added to a solution of 73 mg (0.2 mmol) of 4-(5-Azido-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester (17) and 14 mg (0.2 mmol) of methyl propargyl ether in 4 ml of water/tert-butanol (1/1). The mixture was stirred for 18 h at room temperature. Then ethyl acetate was added and the mixture was filtered through a Celite cartridge. After removal of the solvents the remainder was subjected to preparative HPLC. The N-Boc-protected intermediate was deprotected by treatment with 2 mL 5-6 N HCl in isopropanol for 2 h at room temperature. Then the solvent was evaporated and the product was isolated by preparative HPLC to yield 2.8 mg compound 33 as trifluoroacetate.

Workup

  1. filtrationthe mixture was filtered through a Celite cartridge
  2. customAfter removal of the solvents the remainder
  3. waitwas deprotected by treatment with 2 mL 5-6 N HCl in isopropanol for 2 h at room temperature
  4. customThen the solvent was evaporated
  5. customthe product was isolated by preparative HPLC

Sources & evidence

ORD record
ord-eb2512afe02e47c29f5959b4afb8227f
Source dataset
uspto-grants-2014_05
Patent number
US08722671B2

Reaction notes

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