Propionyl chloride → HCID 57377800, compound

HRID 530045Notes

Reaction equation

HRID 530045 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]([CH3:11])[O:9][CH3:10])[N:5]=[C:4]([NH:12][CH2:13][CH2:14][CH3:15])[N:3]=1.[C:16](Cl)(=[O:19])[CH2:17][CH3:18].CCN(C(C)C)C(C)C>C1COCC1>[CH3:10][O:9][N:8]([CH3:11])[C:6]1[N:5]=[C:4]([NH:12][CH2:13][CH2:14][CH3:15])[N:3]=[C:2]([NH:1][C:16](=[O:19])[CH2:17][CH3:18])[N:7]=1

Participants

5

Reactant 3

HCID 62324Propionyl chlorideHCID 81531DiisopropylethylamineHCID 57377804N2-Methoxy-N2-methyl-N4-propyl-1,3,5-triazine-2,4,6-triamine

Product 1

HCID 57377800HCID 57377800, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

N-(6-amino-4-n-propylamino-[1,3,5]triazin-2-yl)-N,O-dimethyl-hydroxylamine (XXXIX) (5 g, 23.58 mmol) was dissolved in THF (50 mL). Propionyl chloride (3.25 g, 35.38 mmol) and DIPEA (5.47 g, 42.44 mmol) were added at 0° C. The resultant mixture was stirred at ambient temperature for 10 min, then stirred at 70° C. for 16 h, after which time the solvent was removed under reduced pressure. The residue was dissolved in EtOAc (250 mL), and this extract was washed with water (80 mL) and then with a brine solution (80 mL), and lastly dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by flash column chromatography (pet ether/ethyl acetate=5/1 to 2/1) to yield 930 mg (15%) of the desired product. The isolated free amine (930 mg, 3.47 mmol) was dissolved in H2O (10 mL) and 0.5 M HCl solution in H2O (10.4 mL) and then the solution was lyophilized to yield N-(4-(methoxy(methyl)amino)-6-(propylamino)-1,3,5-triazin-2-yl)propionamide (XL) as a colorless oil (1.06 g). LCMS: (ESI) m/z=269 (M+H)+. 1H NMR (500 MHz, DMSO): δ (ppm) 12.23 (s, 1H), 8.25-9.45 (m, 2H), 3.76-3.84 (m, 3H), 3.30-3.44 (m, 5H), 2.55-2.56 (m, 1H), 2.21-2.22 (m, 1H), 1.53-1.58 (m, 2H), 0.88-1.08 (m, 6H).

Workup

  1. customafter which time the solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in EtOAc (250 mL)
  3. washthis extract was washed with water (80 mL)
  4. dry with materialwith a brine solution (80 mL), and lastly dried over Na2SO4
  5. customThe solvent was removed under reduced pressure
  6. customthe crude product was purified by flash column chromatography (pet ether/ethyl acetate=5/1 to 2/1)

Sources & evidence

ORD record
ord-d1840fd7bcb448dd9e20979cebf55ac5
Source dataset
uspto-grants-2016_05
Patent number
US09351972B2

Reaction notes

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