Bromobenzene → t-butyl 2-anilino-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate

HRID 930498Notes

Reaction equation

HRID 930498 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[C:13]([NH2:16])[N:14]=[CH:15][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(O)(C)C.C(Cl)Cl>[NH:16]([C:13]1[N:14]=[CH:15][C:10]2[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:18][CH2:17][C:11]=2[N:12]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 7961BromobenzeneHCID 10796Cesium carbonateHCID 29184118tert-butyl 2-amino-5H,6H,7H,8H-pyrido[4,3-d]pyrimidine-6-carboxylate

Product 1

HCID 45106267t-butyl 2-anilino-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-t-Butoxycarbonyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-ylamine, Intermediate 3 (996 mg, 3.98 mmol), bromobenzene (0.42 mL, 3.98 mmol), Cl-BrettPhos-Pd/BrettPhos 1 mol/1 mol admixture (133 mg, 0.0995 mmol) and cesium carbonate (1.82 g, 5.57 mmol) in t-BuOH (30 mL) was heated at 100° C. for 16 hours. Upon cooling to ambient temperature, the reaction mixture was diluted with CH2Cl2 and the insolubles were filtered off (celite). The filtrate was concentrated and the residue was eluted through a flash column (silica gel 60, 230-400 mesh, 7:3 hexanes:EtOAc) to obtain a yellow glass (770 mg, 59%).

Workup

  1. temperatureUpon cooling to ambient temperature
  2. filtrationthe insolubles were filtered off (celite)
  3. concentrationThe filtrate was concentrated
  4. washthe residue was eluted through a flash column (silica gel 60, 230-400 mesh, 7:3 hexanes:EtOAc)

Sources & evidence

ORD record
ord-d8c60dba33f647f5b3ad01dd5bb3c703
Source dataset
uspto-grants-2016_03
Patent number
US09296747B1

Reaction notes

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