Sodium Bicarbonate → Tert-butyl (S)-3-((5,6,7,8-tetrahydropyrido[4,3-D]pyrimidin-4-YL)amino)pyrrolidine-1-carboxylate

HRID 242317Notes

Reaction equation

HRID 242317 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[C:15]3[CH2:23][N:22](CC4C=CC=CC=4)[CH2:21][CH2:20][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+].C([O-])(O)=O.[Na+]>CO.C(Cl)Cl.CCOC(C)=O.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:14]2[C:15]3[CH2:23][NH:22][CH2:21][CH2:20][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 2723923Ammonium formate2×HCID 574953231-Pyrrolidinecarboxylic acid, 3-[[5,6,7,8-tetrahydro-6-(phenylmethyl)pyrido[4,3-d]pyrimidin-4-yl]amino]-, 1,1-dimethylethyl ester, (3S)-2×

Product 1

HCID 57495324Tert-butyl (S)-3-((5,6,7,8-tetrahydropyrido[4,3-D]pyrimidin-4-YL)amino)pyrrolidine-1-carboxylateYield 66.2%

Reagents, catalysts & solvents 4

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (intermediate 22) (30.1 g, 73.5 mmol) in MeOH (100 mL) was added 20% palladium hydroxide on carbon (3.3 g) then ammonium formate (4.63 g, 73.5 mmol) and the mixture heated at reflux for 1 h. Added ammonium formate (0.38 g, 6.02 mmol) and continued heating at reflux for 30 min. The reaction mixture was allowed to cool and filtered through a celite pad, washing with MeOH (50 mL) then CH2Cl2 (50 mL). The filtrate was evaporated in vacuo to give a brown oil. Dissolved in CH2Cl2 (100 mL), added solid NaHCO3 (10 g) and filtered through a celite pad. The filtrate was evaporated in vacuo to give a brown oil. Dissolved in EtOAc (50 mL) and a solid precipitated which was filtered to give (S)-3-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester as a beige solid (15.55 g, 66% yield). 1H-NMR (400 MHz, DMSO-d6, 298 K): δ ppm 1.40 (s, 9H) 1.81-1.98 (m, 1H) 2.05-2.17 (m, 1H) 2.92 (t, 2H) 3.10-3.46 (m, 5H) 3.49-3.63 (m, 3H) 4.47-4.63 (m, 1H) 6.46 (d, 1H, N—H) 8.25 (s, 1H). LCMS: [M+H]+=320.0, Rt(6)=1.29 min.

Workup

  1. temperatureat reflux for 1 h
  2. temperatureat reflux for 30 min
  3. temperatureto cool
  4. filtrationfiltered through a celite pad
  5. washwashing with MeOH (50 mL)
  6. customThe filtrate was evaporated in vacuo
  7. customto give a brown oil
  8. filtrationfiltered through a celite pad
  9. customThe filtrate was evaporated in vacuo
  10. customto give a brown oil
  11. customa solid precipitated which
  12. filtrationwas filtered

Sources & evidence

ORD record
ord-bb63a14585c540c09954226146462a5e
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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