Potassium Carbonate → 6-Chloro-4-(cyclohexylthio)pyrido[3,2-d]pyrimidine

HRID 1182948Notes

Reaction equation

HRID 1182948 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9](OC3CCOCC3)[C:10]=2[N:11]=1.[CH:19]1([SH:25])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([S:25][CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[C:10]=2[N:11]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 15290CyclohexanethiolHCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 866710706-Chloro-4-(cyclohexylthio)pyrido[3,2-d]pyrimidineYield 92.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.1 g, 0.500 mmol) in ACN (2.500 ml) were added cyclohexanethiol (0.058 g, 0.500 mmol) and K2CO3 (0.069 g, 0.500 mmol) at room temperature. After stiffing overnight at room temperature, the reaction mixture was diluted with water and extracted with EtOAc (2×50 mL). The combined organic layers were washed with 1N aq. NaOH and then washed with 1N aq. HCl. The organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=5:1) to give 6-chloro-4-(cyclo hexylthio)pyrido[3,2-d]pyrimidine (0.129 g, 92%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.36-1.42 (1H, m), 1.48-1.69 (5H, m), 1.80-1.86 (2H, m), 2.14-2.20 (2H, m), 4.10-4.16 (1H, m), 7.73 (1H, d, J=8.8 Hz), 8.19 (1H, d, J=8.8 Hz), 8.98 (1H, s).

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. washThe combined organic layers were washed with 1N aq. NaOH
  3. washwashed with 1N aq. HCl
  4. dry with materialThe organic layers were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=5:1)

Sources & evidence

ORD record
ord-03f6470eef2840ae8045d1d0d76cdf65
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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