Trifluoroacetic acid → 6-benzyl-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

HRID 242334Notes

Reaction equation

HRID 242334 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][C:14]2[C:15]3[CH2:23][N:22]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:21][CH2:20][C:16]=3[N:17]=[CH:18][N:19]=2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:24]([N:22]1[CH2:21][CH2:20][C:16]2[N:17]=[CH:18][N:19]=[C:14]([O:13][C@H:10]3[CH2:11][CH2:12][NH:8][CH2:9]3)[C:15]=2[CH2:23]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57495302(S)-3-(6-Benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 574953476-benzyl-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidineYield 99.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-yloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester (560 mg, 1.364 mmol) in 2 mL of CH2Cl2 was added TFA (1.576 mL, 20.46 mmol). The reaction mixture was stirred at rt for 1 h, concentrated and then eluted through an Isolute SCX-2 cartridge (10 g) to remove excess TFA with (i) MeOH (ii) NH3/MeOH and the basic fraction evaporated in vacuum to give 6-benzyl-4-((S)-pyrrolidin-3-yloxy)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (420 mg, quantitative yield) as a yellow gum. LCMS: [M+H]+=311.2, Rt(3)=0.11.

Workup

  1. concentrationconcentrated
  2. washeluted through an Isolute SCX-2 cartridge (10 g)
  3. customto remove excess TFA with (i) MeOH (ii) NH3/MeOH
  4. customthe basic fraction evaporated in vacuum

Sources & evidence

ORD record
ord-000c6ceed3bd49929b292e79b917bd7c
Source dataset
uspto-grants-2014_02
Patent number
US08653092B2

Reaction notes

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