Ethyl Acetate → HCID 178516345, compound

HRID 1890455Notes

Reaction equation

HRID 1890455 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH2:9].[N:10]1([C:16]2[N:17]=[C:18]([CH2:23][C:24]([O-])=O)[NH:19][C:20](=[O:22])[CH:21]=2)[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.[Na+].O.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.C(OCC)(=O)C>CO>[F:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:24]([CH2:23][C:18]3[NH:19][C:20](=[O:22])[CH:21]=[C:16]([N:10]4[CH2:15][CH2:14][O:13][CH2:12][CH2:11]4)[N:17]=3)=[N:9][C:3]=2[CH:4]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 1645844-Fluorobenzene-1,2-diamineHCID 231494114-(4,6-Dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrateHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 178516345HCID 178516345, compoundYield 42.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

151 mg of 1,2-diamino-4-fluorobenzene are added to a solution of 261 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in 8 ml of methanol. The resulting mixture is stirred at ambient temperature for 5 minutes and then 354 mg of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride hydrate are added. The resulting mixture is thus stirred for 30 minutes at ambient temperature. The reaction mixture is then concentrated to dryness under reduced pressure, and the residue is then taken up in 30 ml of acetic acid. The reaction mixture is brought to reflux for 1 hour, and then concentrated under reduced pressure. 30 ml of water are then added and a saturated aqueous solution of sodium bicarbonate is added until a pH in the region of 7 is obtained. 20 ml of ethyl acetate are then added and the resulting mixture is stirred for 1 hour. The precipitate formed is filtered off and subsequently purified by silica gel column chromatography, elution being carried out with a gradient of the eluent CH2Cl2/MeOH: 80/20 in dichloromethane of 0% to 100% in 25 minutes. 140 mg of 2-[(5-fluoro-1H-benzimidazol-2-yl)methyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of an off-white solid, the characteristics of which are the following:

Workup

  1. stirringThe resulting mixture is thus stirred for 30 minutes at ambient temperature
  2. concentrationThe reaction mixture is then concentrated to dryness under reduced pressure
  3. temperatureto reflux for 1 hour
  4. concentrationconcentrated under reduced pressure
  5. addition30 ml of water are then added
  6. additiona saturated aqueous solution of sodium bicarbonate is added until a pH in the region of 7
  7. customis obtained
  8. stirringthe resulting mixture is stirred for 1 hour
  9. customThe precipitate formed
  10. filtrationis filtered off
  11. customsubsequently purified by silica gel column chromatography, elution
  12. wait80/20 in dichloromethane of 0% to 100% in 25 minutes

Sources & evidence

ORD record
ord-8b0c00d86f4b417cad28ab9e75454369
Source dataset
uspto-grants-2013_08
Patent number
US08507483B2

Reaction notes

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