Cyclopropylamine → 6-chloro-N-cyclopropylpyrido[3,2-d]pyrimidin-4-amine

HRID 1182953Notes

Reaction equation

HRID 1182953 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([NH2:22])[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:22][CH:19]3[CH2:21][CH2:20]3)[C:10]=2[N:11]=1

Participants

5

Reactant 3

HCID 69828CyclopropylamineHCID 23676156Sodium t-butoxideHCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 866710756-chloro-N-cyclopropylpyrido[3,2-d]pyrimidin-4-amineYield 54.4%

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), cyclopropanamine (0.038 ml, 0.550 mmol), PdCl2(dppf)-CH2Cl2Adduct (4.08 mg, 5.00 μmmol) and sodium tert-butoxide (0.096 g, 1.00 mmol) in dioxane (2.50 ml) was refluxed for 4 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-cyclopropylpyrido[3,2-d]pyrimidin-4-amine (0.060 g, 54%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 0.76-0.79 (2H, m), 0.99-1.03 (2H, m), 3.02-3.06 (1H, m), 7.12 (1H, brs), 7.61-7.63 (1H, m), 8.04-8.07 (1H, m), 8.73 (1H, s).

Workup

  1. temperaturewas refluxed for 4 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-296cacd4d9394260b0c2700e4b8cea22
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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