1,1'-Carbonyldiimidazole → tert-Butyl 4-(1-(2,4-dimethoxybenzyl)-1,2-dihydro-2-oxopyrido[2,3-d]pyrimidin-3(4H)-yl)piperidine-1-carboxylate

HRID 1695895Notes

Reaction equation

HRID 1695895 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:4]=1[CH2:5][NH:6][C:7]1[C:12]([CH2:13][NH:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)=[CH:11][CH:10]=[CH:9][N:8]=1.C1N=CN([C:39](N2C=NC=C2)=[O:40])C=1>CN(C=O)C.O>[CH3:1][O:2][C:3]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:4]=1[CH2:5][N:6]1[C:7]2[N:8]=[CH:9][CH:10]=[CH:11][C:12]=2[CH2:13][N:14]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[C:39]1=[O:40]

Participants

5

Reactant 2

HCID 682631,1'-Carbonyldiimidazole2×HCID 22293293Tert-butyl 4-((2-(2,4-dimethoxybenzylamino)pyridin-3-yl)methylamino)piperidine-1-carboxylate

Product 1

HCID 22293273tert-Butyl 4-(1-(2,4-dimethoxybenzyl)-1,2-dihydro-2-oxopyrido[2,3-d]pyrimidin-3(4H)-yl)piperidine-1-carboxylateYield 38.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of tert-butyl 4-((2-(2,4-dimethoxybenzylamino)pyridin-3-yl)methylamino)piperidine-1-carboxylate (2.89 g, 6.33 mmol) in DMF (42 ml) was added CDI (1.23 g, 7.6 mmol) in portions and the reaction mixture was stirred at 120° C. for 2 hours. A further portion of CDI was added (0.82 g) was added and the reaction mixture stirred at 130° C. for 6 hours, followed by stirring at RT for 16 hours. The reaction was diluted with water and extracted with DCM. The organics were combined, dried (NaSO4) and evaporated to dryness. Purification by column chromatography (10 to 80% EtOAc in Hx) gave the desired product (1.17 g). LC/MS (10% to 99%): M/Z (M+H)+ (obs)=483; tR=3.58.

Workup

  1. additionwas added
  2. stirringthe reaction mixture stirred at 130° C. for 6 hours
  3. stirringby stirring at RT for 16 hours
  4. extractionextracted with DCM
  5. dry with materialdried (NaSO4)
  6. customevaporated to dryness
  7. customPurification by column chromatography (10 to 80% EtOAc in Hx)

Sources & evidence

ORD record
ord-e87ffc183e644bbb9247619e4eb1c21b
Source dataset
uspto-grants-2012_04
Patent number
US08163737B2

Reaction notes

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