Toluene → benzyl 4'-oxo-6'-(pyridin-4-yl)-3',4'-dihydro-1'H-spiro[piperidine-4,2'-thieno[3,2-d]pyrimidine]-1-carboxylate

HRID 2363933Notes

Reaction equation

HRID 2363933 reaction equation
[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([NH2:15])=[O:14].O=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:24])[CH2:19][CH2:18]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>C(O)(=O)C>[O:14]=[C:13]1[NH:15][C:17]2([CH2:22][CH2:21][N:20]([C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[O:24])[CH2:19][CH2:18]2)[NH:1][C:2]2[CH:6]=[C:5]([C:7]3[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=3)[S:4][C:3]1=2

Participants

6

Reactant 4

HCID 1140TolueneHCID 521998p-Toluenesulfonic acid monohydrateHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 99208523-Amino-5-(pyridin-4-yl)thiophene-2-carboxamide

Product 1

HCID 66743981benzyl 4'-oxo-6'-(pyridin-4-yl)-3',4'-dihydro-1'H-spiro[piperidine-4,2'-thieno[3,2-d]pyrimidine]-1-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-amino-5-(pyridin-4-yl)thiophene-2-carboxamide (0.219 g, 1.00 mmol), benzyl 4-oxo-1-piperidinecarboxylate (0.700 g, 3.00 mmol), p-toluenesulfonic acid monohydrate (0.211 g, 1.10 mmol) and toluene (10.0 mL) was stirred for 2 h at 90° C. Then, acetic acid (10.0 mL) was added, and the mixture was stirred for 1 h at 80° C. After removal of the solvent at reduced pressure, the obtained residue was poured into aqueous sodium hydrogen carbonate (200 mL). Extraction with ethyl acetate (200 mL, 100 mL), drying over magnesium sulfate, filtration and concentration at reduced pressure gave a solid. The solid was triturated with ethyl acetate/dichloromethane (1:1, 10 mL), and the precipitate was collected by filtration to afford the title compound (0.276 g, 64%) as a yellow solid:

Workup

  1. stirringthe mixture was stirred for 1 h at 80° C
  2. customAfter removal of the solvent at reduced pressure
  3. additionthe obtained residue was poured into aqueous sodium hydrogen carbonate (200 mL)
  4. extractionExtraction with ethyl acetate (200 mL, 100 mL)
  5. dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
  6. customgave a solid
  7. customThe solid was triturated with ethyl acetate/dichloromethane (1:1, 10 mL)
  8. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-3c2d0f85342441a5afe45ddb1082ba91
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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