Triethylamine → Tert-butyl 3-{7-[2-(benzyloxy)phenyl]-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl}-1-piperidinecarboxylate

HRID 2115687Notes

Reaction equation

HRID 2115687 reaction equation
[NH2:1][C:2]1[C:7]([C:8](=[O:10])[NH2:9])=[C:6]([CH:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:3]=1.C(N(CC)CC)C.Cl[C:46](Cl)([O:48]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[CH2:31]([O:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:4]1[CH:5]=[C:6]([CH:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12]2)[C:7]2[C:8](=[O:10])[NH:9][C:46](=[O:48])[NH:1][C:2]=2[N:3]=1)[C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 22258771Tert-butyl 3-{2-amino-6-[2-(benzyl-oxy)phenyl]-3-carbamoyl-4-pyridinyl}-1-piperidinecarboxylate

Product 1

HCID 22258892Tert-butyl 3-{7-[2-(benzyloxy)phenyl]-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl}-1-piperidinecarboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.), stirred solution of tert-butyl 3-{2-amino-6-[2-(benzyloxy)phenyl]-3-carbamoyl-4-pyridinyl}-1-piperidinecarboxylate (0.400 g, 0.800 mmol), which was obtained in the step (1) of Example 7-1, in THF (10 mL) were added triethylamine (0.50 mL, 3.58 mmol) followed by triphosgene (0.354 g, 1.19 mmol). The reaction mixture was stirred at room temperature for 12 hrs. The reaction was quenched with water and extracted with ethyl acetate. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-1/1) and recrystallized from ethanol to give tert-butyl 3-{7-[2-(benzyloxy)phenyl]-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl}-1-piperidinecarboxylate as a white solid. (0.406 g, yield; 97%)

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1-1/1)
  8. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-ca7a65fa046348c0935ec69bf03110e4
Source dataset
uspto-grants-2008_10
Patent number
US07435743B2

Reaction notes

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