Dimethylamine → 3-[4-chloro-2-fluoro-5-(phenylmethoxy)-phenyl]-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione

HRID 1450167Notes

Reaction equation

HRID 1450167 reaction equation
C(O[C:4]([N:6]([CH3:12])[C:7]([NH:10]C)=[N:8][CH3:9])=[O:5])C.[Cl:13][C:14]1[C:19]([O:20]CC2C=CC=CC=2)=[CH:18][C:17]([N:28]=[C:29]=[O:30])=[C:16]([F:31])[CH:15]=1.[CH3:32]NC.[C:35]1([CH3:41])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C[O-].[Na+]>[Cl:13][C:14]1[C:19]([O:20][CH2:41][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:18][C:17]([N:28]2[C:29](=[O:30])[N:10]=[C:7]([N:8]([CH3:32])[CH3:9])[N:6]([CH3:12])[C:4]2=[O:5])=[C:16]([F:31])[CH:15]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 1140Toluene4×HCID 199752544-Chloro-2-fluoro-5-(phenylmethoxy)phenyl isocyanateHCID 45122948N-ethoxycarbonyl-N,N', N"-trimethylguanidine

Product 1

HCID 199752643-[4-chloro-2-fluoro-5-(phenylmethoxy)-phenyl]-6-(dimethylamino)-1-methyl-1,3,5-triazine-2,4(1H,3H)-dione

Reagents, catalysts & solvents 1

HCID 10942334Sodium MethoxideCatalyst

Procedure

To a solution of 5.05 g (29.2 mmol) of N-ethoxycarbonyl-N,N', N"-trimethylguanidine in 25 mL of toluene was added a solution of 7.72 g (27.8 mmol) of 4-chloro-2-fluoro-5-(phenylmethoxy)phenyl isocyanate in 50 mL of toluene over a period of 30 min while maintaining the temperature between 55° C. and 80° C. It was then stirred at the same temperature for an hour. To a solution of the resulting N-[N-[4-chloro-2-fluoro-5-(phenylmethoxy) phenyl]carbamoyl-N',N'-dimethylamidino]-N-methylcarbamate in toluene was added 3.21 g (71.5 mmol) of dimethylamine in 10 mL of toluene at room temperature. While the temperature was between 25° C. and 40° C., 45 mg (0.834 mmol) of sodium methoxide was added. After 30 min, it was quenched with 100 mL of water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with 0.1N hydrochloric acid, brine, and water, dried (MgSO4) and concentrated in vacuo. The crude product was flash chromatographed over silica gel eluting with a 1:1 v:v mixture of ethyl acetate and hexane to give 5.3 g of the title compound as a brown solid, m.p.: 193°-194° C.; 1H-NMR (CDCl3, 200 MHZ) ppm 7.4 (m, 6H), 6.95 (d, 1H), 5.05 (d, 2H), 3.45 (s, 3H), 3.1 (s, 6H).

Workup

  1. temperaturewhile maintaining the temperature between 55° C. and 80° C
  2. customwas between 25° C. and 40° C.
  3. customit was quenched with 100 mL of water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with 0.1N hydrochloric acid, brine, and water
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customchromatographed over silica gel eluting with a 1:1 v
  9. additionv mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-0dd4c6ba757a4f4eb296ba3f8406f796
Source dataset
uspto-grants-1997_02
Patent number
US05602077

Reaction notes

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