Triethylamine → (E)-ethyl 3-(2-amino-4-methyl-6-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-5-yl)acrylate

HRID 421997Notes

Reaction equation

HRID 421997 reaction equation
I[C:2]1[C:3]([NH:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[N:4][C:5]([NH2:9])=[N:6][C:7]=1[CH3:8].C(N(CC)CC)C.[C:24]([O:28][CH2:29][CH3:30])(=[O:27])[CH:25]=[CH2:26]>CN(C=O)C>[NH2:9][C:5]1[N:6]=[C:7]([CH3:8])[C:2](/[CH:26]=[CH:25]/[C:24]([O:28][CH2:29][CH3:30])=[O:27])=[C:3]([NH:10][CH:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:4]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 592727355-iodo-6-methyl-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4-diamine

Product 1

HCID 59272733(E)-ethyl 3-(2-amino-4-methyl-6-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-5-yl)acrylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 5-iodo-6-methyl-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4-diamine (10.0 g, 30.0 mmol) in DMF (200 mL) was added triethylamine (12.50 mL, 90.0 mmol) and ethyl acrylate (9.80 mL, 90.0 mmol) successively at room temperature. The reaction was purged with nitrogen for 5 min. and Pd(PPh3)4 (10 mol %, 3.50 g) was added. The reaction was heated to 95° C., stirred for overnight under nitrogen, and then cooled to room temperature. Nearly all DMF was evaporated under reduced pressure. The reaction was poured into ethyl acetate (500 mL) and H2O (300 mL). The organic layer collected and dried over anhydrous sodium sulfate, and concentrated in vacuo to afford the crude product. The product was purified by a flash chromatography (70% ethyl acetate/hexanes to 10% EtOH/ethyl acetate) to afford (E)-ethyl 3-(2-amino-4-methyl-6-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-5-yl)acrylate, as a light yellow semicrystal (yield: 6.85 g, 75.0%). LC/MS: calculated for C15H22N4O3 (306.17). found: 307.2 (MH+). HPLC analytical purity: >97.0%.

Workup

  1. customThe reaction was purged with nitrogen for 5 min.
  2. additionPd(PPh3)4 (10 mol %, 3.50 g) was added
  3. temperaturecooled to room temperature
  4. customNearly all DMF was evaporated under reduced pressure
  5. additionThe reaction was poured into ethyl acetate (500 mL) and H2O (300 mL)
  6. customThe organic layer collected
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto afford the crude product
  10. customThe product was purified by a flash chromatography (70% ethyl acetate/hexanes to 10% EtOH/ethyl acetate)

Sources & evidence

ORD record
ord-28104112c73941afa2bcb157131547ef
Source dataset
uspto-grants-2012_01
Patent number
US08101622B2

Reaction notes

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