Water → HCID 66653470, compound

HRID 409545Notes

Reaction equation

HRID 409545 reaction equation
Cl.[Cl:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.C(=O)([O-])[O-].[K+].[K+].[F:17][C:18]1[CH:57]=[CH:56][C:21]([CH2:22][N:23]2[C:32](=[O:33])[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([C:34]([C:36]4[N:40]5[CH:41]=[CH:42][CH:43]=[CH:44][C:39]5=[C:38]([C:45]5[CH:46]=[C:47]([CH:51]=[CH:52][CH:53]=5)[C:48]([OH:50])=[O:49])[N:37]=4)=[O:35])[CH:30]=3)[N:25]([CH3:54])[C:24]2=[O:55])=[CH:20][CH:19]=1.O>CN(C=O)C.CCOCC>[ClH:2].[F:17][C:18]1[CH:57]=[CH:56][C:21]([CH2:22][N:23]2[C:32](=[O:33])[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([C:34]([C:36]4[N:40]5[CH:41]=[CH:42][CH:43]=[CH:44][C:39]5=[C:38]([C:45]5[CH:46]=[C:47]([CH:51]=[CH:52][CH:53]=5)[C:48]([O:50][CH2:3][CH2:4][N:5]5[CH2:10][CH2:9][O:8][CH2:7][CH2:6]5)=[O:49])[N:37]=4)=[O:35])[CH:30]=3)[N:25]([CH3:54])[C:24]2=[O:55])=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 77210Morpholine, 4-(2-chloroethyl)-, hydrochloride (1:1)HCID 54768042HCID 54768042, compound

Product 1

HCID 66653470HCID 66653470, compoundYield 77.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

0.022 g (0.61 mmol) of 4-(2-chloroethyl)morpholine hydrochloride and 0.189 g (1.37 mmol) of potassium carbonate are added, under an inert atmosphere, to 0.3 g (0.55 mmol) of 3-(3-{[3-(4-fluorobenzyl)-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl]carbonyl}imidazo[1,5-a]pyridin-1-yl)benzoic acid in 8 ml of DMF. After stirring for 18 h at ambient temperature and then for 8 hours at 50° C., the reaction medium is hydrolysed with water, and extracted with ethyl acetate. The organic phase is washed with water, dried over sodium sulphate, filtered, and then concentrated under reduced pressure. The yellow solid obtained is purified by silica gel column chromatography, elution being carried out with a dichloromethane/methanol (95/5) mixture. 0.61 ml of a 1N aqueous solution of hydrochloric acid is added to 0.334 g of the yellow solid obtained, in 5 ml of methanol. The reaction medium is stirred for 1 hour at ambient temperature. Dyethyl ether is added and then the reaction medium is filtered. The precipitate obtained is rinsed with dyethyl ether and then dried under reduced pressure at 50° C. overnight. 0.298 g of a yellow solid is obtained.

Workup

  1. waitfor 8 hours at 50° C.
  2. extractionextracted with ethyl acetate
  3. washThe organic phase is washed with water
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe yellow solid obtained
  8. customis purified by silica gel column chromatography, elution
  9. addition0.61 ml of a 1N aqueous solution of hydrochloric acid is added to 0.334 g of the yellow solid
  10. customobtained, in 5 ml of methanol
  11. stirringThe reaction medium is stirred for 1 hour at ambient temperature
  12. filtrationthe reaction medium is filtered
  13. customThe precipitate obtained
  14. washis rinsed with dyethyl ether
  15. customdried under reduced pressure at 50° C. overnight

Sources & evidence

ORD record
ord-0759b52ac9fc4164a672d6ac007404ee
Source dataset
uspto-grants-2014_06
Patent number
US08759344B2

Reaction notes

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