Morpholine → HCID 57677494, compound

HRID 492780Notes

Reaction equation

HRID 492780 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])=[C:11]([F:28])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.Cl[C:37](OC1C=CC=CC=1)=[O:38].[NH:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>O1CCCC1.C(OCC)C.CN(C)C=O>[F:28][C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][C:12]=1[NH:15][C:16]([NH:18][C:19](=[O:27])[CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[S:17])[O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:37]([N:46]2[CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)=[O:38])[CH:7]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 23153220HCID 23153220, compound

Product 1

HCID 57677494HCID 57677494, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]-3-(2-phenylacetyl)thiourea (270 mg) in tetrahydrofuran (12 ml) was added triethylamine (0.142 ml), and then phenyl chloroformate (0.160 ml) was added while stirring in an ice bath, followed by stirring under a nitrogen atmosphere for 30 min. A portion of the solution (4.0 ml) was concentrated under a reduced pressure, and then N,N-dimethylformamide (1.5 ml) and morpholine (0.989 ml, 1.14 mmol) were added thereto, followed by stirring at room temperature for 5 hrs. The reaction mixture was partitioned between ethyl acetate (40 ml) and water (40 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1, ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing the target compound were concentrated to give a solid, which was suspended in diethyl ether. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (42 mg) as pale brown powder.

Workup

  1. stirringby stirring under a nitrogen atmosphere for 30 min
  2. concentrationA portion of the solution (4.0 ml) was concentrated under a reduced pressure
  3. stirringby stirring at room temperature for 5 hrs
  4. customThe reaction mixture was partitioned between ethyl acetate (40 ml) and water (40 ml)
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (eluent
  10. additionFractions containing the target compound
  11. concentrationwere concentrated
  12. customto give a solid, which
  13. filtrationThe solid was filtered off
  14. washwashed with diethyl ether
  15. customdried under aeration

Sources & evidence

ORD record
ord-7ec0faa0fc27463aa5ad0dfc686a3a22
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…