4-Aminopyridine → 1-Cyclopropyl-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]propan-2-one

HRID 2359748Notes

Reaction equation

HRID 2359748 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:18]1([CH2:21][C:22](=[O:33])[CH2:23][C:24]2[CH:29]=[CH:28][N:27]=[C:26](S(C)=O)[N:25]=2)[CH2:20][CH2:19]1>C1COCC1>[CH:18]1([CH2:21][C:22](=[O:33])[CH2:23][C:24]2[CH:29]=[CH:28][N:27]=[C:26]([NH:1][C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[N:25]=2)[CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 17274-AminopyridineHCID 2733832Lithium HexamethyldisilazideHCID 679834701-Cyclopropyl-3-[2-(methylsulfinyl)pyrimidin-4-yl]propan-2-one

Product 1

HCID 679838261-Cyclopropyl-3-[2-(pyridin-4-ylamino)pyrimidin-4-yl]propan-2-oneYield 86.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-aminopyridine (328 mg, 3.49 mmol) in THF (2.344 mL) cooled to −78° C. was added LHMDS (583 mg, 3.49 mmol). The reaction was warmed to rt and stirred for 15 minutes. The reaction was again cooled to −78° C. and 1-cyclopropyl-3-[2-(methylsulfinyl)pyrimidin-4-yl]propan-2-one (7) (277 mg, 1.162 mmol) was added as a solution in THF (2 mL). The reaction was warmed to rt and stirred for 1 hour. The reaction was quenched by slow addition of saturated ammonium chloride and the volatiles evaporated. The residue was then partitioned between water and DCM. The organic layer was washed with brine, dried with sodium sulfate, and concentrated in vacuo. The crude residue was purified by Biotage™ silica gel chromatography [2-10% MeOH in DCM with 1% triethylamine] to afford the desired product as a yellow oil (269 mg, 86%). MS (ES+): m/z=269.2 (100) [MH+2]. HPLC: tR=0.69 minute over 3 minutes. Purity: >95% [HPLC (LC/MS) at 220 nm].

Workup

  1. temperatureThe reaction was again cooled to −78° C.
  2. temperatureThe reaction was warmed to rt
  3. stirringstirred for 1 hour
  4. customThe reaction was quenched by slow addition of saturated ammonium chloride
  5. customthe volatiles evaporated
  6. customThe residue was then partitioned between water and DCM
  7. washThe organic layer was washed with brine
  8. dry with materialdried with sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by Biotage™ silica gel chromatography [2-10% MeOH in DCM with 1% triethylamine]

Sources & evidence

ORD record
ord-74928b1afcee4a2a9749c81d53210e62
Source dataset
uspto-grants-2014_04
Patent number
US08685993B2

Reaction notes

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