Ammonium formate → 3-(5,6,7,8-Tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-azetidine-1-carboxylic acid tert-butyl ester

HRID 242331Notes

Reaction equation

HRID 242331 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[C:14]3[CH2:22][N:21](CC4C=CC=CC=4)[CH2:20][CH2:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[C:14]3[CH2:22][NH:21][CH2:20][CH2:19][C:15]=3[N:16]=[CH:17][N:18]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 574953443-(6-Benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 574953433-(5,6,7,8-Tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-azetidine-1-carboxylic acid tert-butyl esterYield 67.1%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of 3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-azetidine-1-carboxylic acid tert-butyl ester (425 mg, 1.07 mmol) in MeOH (20 mL) was added 20% palladium hydroxide on carbon (90 mg) then ammonium formate (473 mg, 7.51 mmol) and the mixture heated at reflux for 1 h. The reaction mixture was allowed to cool and filtered through a celite pad, washing with MeOH (20 mL) then CH2Cl2 (20 mL). The filtrate was evaporated in vacuo and purified by flash chromatography on silica gel with CH2Cl2/MeOH/0.88 NH4OH, 100/0/0 to 90/10/1 to give 3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-azetidine-1-carboxylic acid tert-butyl ester as a yellow gum (220 mg, 67% yield) LCMS: [M+H]+=307.3, Rt(4)=0.81 min.

Workup

  1. temperatureat reflux for 1 h
  2. temperatureto cool
  3. filtrationfiltered through a celite pad
  4. washwashing with MeOH (20 mL)
  5. customThe filtrate was evaporated in vacuo
  6. custompurified by flash chromatography on silica gel with CH2Cl2/MeOH/0.88 NH4OH, 100/0/0 to 90/10/1

Sources & evidence

ORD record
ord-5b1cc647654e42a2a618d1008838061e
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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