4-Methylmorpholine → HCID 57677483, compound

HRID 492796Notes

Reaction equation

HRID 492796 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19](=[O:27])[CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[S:17])=[CH:11][C:10]=2[F:28])[CH:5]=[CH:4][N:3]=1.CN1CC[O:33][CH2:32]C1.ClC(OC1C=CC=CC=1)=O.O.Cl.[O:48]=[C:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1>O1CCCC1.CN(C)C=O>[F:28][C:10]1[CH:11]=[C:12]([NH:15][C:16]([NH:18][C:19](=[O:27])[CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[S:17])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:32]([N:52]2[CH2:53][CH2:54][C:49](=[O:48])[CH2:50][CH2:51]2)=[O:33])[CH:7]=1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 15891Phenyl chloroformateHCID 2723901PiperonylamineHCID 576774122-Amino-4-{2-fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}pyridine

Product 1

HCID 57677483HCID 57677483, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-4-{2-fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}pyridine (100 mg) was dissolved in tetrahydrofuran (2.5 ml) under a nitrogen atmosphere, and then N-methylmorpholine (0.080 ml) and phenyl chloroformate (0.080 ml) were added dropwise thereto while cooling in an ice bath, followed by raising the temperature up to room temperature and stirring for 20 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then dissolved in N,N-dimethylformamide (2.5 ml), and then N-methylmorpholine (0.2 ml) and 4-oxopiperidine hydrochloride monohydrate (272 mg) were added thereto at room temperature, followed by stirring for 23 hrs. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; ethyl acetate). Fractions containing the target compound were concentrated under a reduced pressure to give a residue, which was dried in vacuum to provide the titled compound (83.1 mg, 63%) as white powder.

Workup

  1. temperaturewhile cooling in an ice bath
  2. customThe reaction mixture was partitioned between ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customat room temperature
  8. stirringby stirring for 23 hrs
  9. customThe reaction mixture was partitioned between ethyl acetate
  10. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  11. dry with materialdried over anhydrous sodium sulfate
  12. customThe solvent was evaporated
  13. customto give a residue, which
  14. customwas then purified by silica gel column chromatography (eluent; ethyl acetate)
  15. additionFractions containing the target compound
  16. concentrationwere concentrated under a reduced pressure
  17. customto give a residue, which
  18. customwas dried in vacuum

Sources & evidence

ORD record
ord-c5a1705d891b4efc8b0aa40339f51ab0
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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