Hydrochloric Acid → 3-(4,6-diethoxy-1,3,5-triazin-2-yl)-7-fluoro-1,3-dihydro-2H-indol-2-one

HRID 1854777Notes

Reaction equation

HRID 1854777 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[CH2:7]2.C(=O)([O-])[O-].[K+].[K+].[OH-].[K+].Cl[C:21]1[N:26]=[C:25]([O:27][CH2:28][CH3:29])[N:24]=[C:23]([O:30][CH2:31][CH3:32])[N:22]=1.Cl>CN(C)C(=O)C.O.C1(C)C=CC=CC=1>[CH2:28]([O:27][C:25]1[N:24]=[C:23]([O:30][CH2:31][CH3:32])[N:22]=[C:21]([CH:7]2[C:6]3[C:10](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=3)[NH:9][C:8]2=[O:11])[N:26]=1)[CH3:29]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 356492-Chloro-4,6-diethoxy-1,3,5-triazine2×HCID 37343717-Fluoro-2,3-dihydro-1h-indol-2-one

Product 1

HCID 679826823-(4,6-diethoxy-1,3,5-triazin-2-yl)-7-fluoro-1,3-dihydro-2H-indol-2-one

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 31374DimethylacetamideSolvent2×

Procedure

7-Fluoro-1,3-dihydro-2H-indol-2-one (1.0 g) is introduced as initial charge in 10 ml of N,N-dimethylacetamide. A solution of potassium carbonate (1.8 g) and potassium hydroxide (0.3 g) in 10 ml of water is added and the mixture is briefly after-stirred. Then, a solution of 2-chloro-4,6-diethoxy-1,3,5-triazine (3.0 g, ca. 50% purity) in 10 ml of N,N-dimethylacetamide, and 10 ml of water are added. A solid separates out from the clear yellow solution. The mixture is stirred at room temperature and further 2-chloro-4,6-diethoxy-1,3,5-triazine (1 g, ca. 50% purity) is added in two portions after 2 and 18 hours. The mixture is stirred for a further 3 hours at 30° C., admixed with 10 ml of toluene, adjusted to pH 1-2 with hydrochloric acid (10%) and after-stirred for 30 min. The solid is filtered off with suction, washed twice alternately with water and heptane and dried. This gives the title compound as solid in an HPLC purity of 99% area (1.53 g, 72% of theory).

Workup

  1. stirringThe mixture is stirred at room temperature
  2. stirringThe mixture is stirred for a further 3 hours at 30° C.
  3. stirringafter-stirred for 30 min
  4. filtrationThe solid is filtered off with suction
  5. washwashed twice alternately with water and heptane
  6. customdried

Sources & evidence

ORD record
ord-722cf645e6d04bd7bff1e3163778ae74
Source dataset
uspto-grants-2015_02
Patent number
US08962828B2

Reaction notes

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