Dimethyl Sulfate → 2-fluoro-N-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-9-methyl-9H-purin-6-amine

HRID 928175Notes

Reaction equation

HRID 928175 reaction equation
[F:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([NH:11][C:12]2[C:13]([O:18][CH3:19])=[N:14][N:15]([CH3:17])[CH:16]=2)[N:3]=1.[C:20](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>O1CCOCC1>[F:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:20])=[C:4]([NH:11][C:12]2[C:13]([O:18][CH3:19])=[N:14][N:15]([CH3:17])[CH:16]=2)[N:3]=1

Participants

5

Reactant 3

HCID 6497Dimethyl Sulfate2×HCID 11430Potassium Carbonate2×HCID 178494310HCID 178494310, compound

Product 1

HCID 1180735462-fluoro-N-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-9-methyl-9H-purin-6-amineYield 84.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a vigorously stirred suspension of 2-fluoro-N-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-9H-purin-6-amine (7.25 g, 27.5 mmol, 1.00 eq) and potassium carbonate (7.61 g, 55.1 mmol, 2.00 eq) in 1,4-dioxane (92.0 mL), was added dimethyl sulfate (2.90 mL, 30.3 mmol, 1.10 eq) in a dropwise manner over 3 min. After 4 hr, additional portions of 1,4-dioxane (50.0 mL), potassium carbonate (3.80 g, 27.5 mmol, 1.00 eq), and dimethyl sulfate (1.00 mL, 10.4 mmol, 0.30 eq) were added to the reaction mixture. After a further 16 hr, the reaction mixture was concentrated in vacuo, diluted with water (120 mL), and stirred at ambient temperature for 1 hr. The resulting solids were filtered, washed with water (20 mL), and dried for 16 hr at 60° C. to give the title compound (6.42 g, 84% yield, >95% purity) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.23 (br. s., 1 H) 8.13 (br. s., 1 H) 7.67 (s, 1 H) 3.78 (s, 3 H) 3.70 (s, 3 H) 3.69 (br. s., 3 H). m/z (APCI+) for C11H13FN7O 278.2 (M+H)+.

Workup

  1. waitAfter a further 16 hr
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. additiondiluted with water (120 mL)
  4. filtrationThe resulting solids were filtered
  5. washwashed with water (20 mL)
  6. customdried for 16 hr at 60° C.

Sources & evidence

ORD record
ord-96b0720b1eb2450a9d865699f928c448
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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