Cyclopentylamine → 6-chloro-N-cyclopentylpyrido[3,2-d]pyrimidin-4-amine

HRID 1182951Notes

Reaction equation

HRID 1182951 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([NH2:24])[CH2:23][CH2:22][CH2:21][CH2:20]1.CC(C)([O-])C.[Na+]>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:24][CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[C:10]=2[N:11]=1

Participants

5

Reactant 3

HCID 2906CyclopentylamineHCID 23676156Sodium t-butoxideHCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 866710736-chloro-N-cyclopentylpyrido[3,2-d]pyrimidin-4-amineYield 35%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.100 g, 0.500 mmol), cyclopentanamine (0.054 ml, 0.550 mmol), PdCl2(dppf)-CH2Cl2Adduct (4.08 mg, 5.00 mmol) and sodium tert-butoxide (0.096 g, 1.00 mmol) in dioxane (2.50 ml) was refluxed for 3 hours. After cooling to room temperature, the reaction mixture was filtered through a Celite pad and washed with CH2Cl2. The filtrate was concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give 6-chloro-N-cyclopentylpyrido[3,2-d]pyrimidin-4-amine (0.043 g, 35%) as a yellow oil. 1H-NMR (CDCl3, Varian 400 MHz)): δ 1.60-1.83 (6H, m), 2.15-2.21 (2H, m), 4.55-4.60 (1H, m), 6.96 (1H, d, J=6.4 Hz), 7.59-7.62 (1H, m), 8.02-8.04 (1H, m), 8.63 (1H, s).

Workup

  1. temperaturewas refluxed for 3 hours
  2. filtrationthe reaction mixture was filtered through a Celite pad
  3. washwashed with CH2Cl2
  4. concentrationThe filtrate was concentrated in vacuo
  5. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

Sources & evidence

ORD record
ord-c527c87de3cf4494bcbd58f422a6423a
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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