4-Methylmorpholine → HCID 57677582, compound

HRID 492799Notes

Reaction equation

HRID 492799 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.[N:46]1([CH:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)[CH2:50][CH2:49][CH2:48][CH2:47]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:54]2[CH2:55][CH2:56][CH:51]([N:46]3[CH2:50][CH2:49][CH2:48][CH2:47]3)[CH2:52][CH2:53]2)=[O:33])[CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 15891Phenyl chloroformateHCID 787034-(1-Pyrrolidinyl)piperidineHCID 576774122-Amino-4-{2-fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}pyridine

Product 1

HCID 57677582HCID 57677582, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-4-{2-fluoro-4-[3-(2-phenylacetyl)thioureido]phenoxy}pyridine (66.6 mg) was dissolved in tetrahydrofuran (2.0 ml) under a nitrogen atmosphere, and then N-methylmorpholine (0.0462 ml) and phenyl chloroformate (0.0527 ml) in this order were added dropwise thereto while cooling in an ice bath, followed by raising the temperature up to room temperature and stirring for 15 min. The solvent was evaporated to give a residue, which was dissolved in N,N-dimethylformamide (2.0 ml), and then 4-(pyrrolidin-1-yl)piperidine (136 mg) was added thereto at room temperature, followed by stirring for 2 hr. 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 (Fuji Silysia NH, eluent; ethyl acetate:methanol=95:5). 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 (46.3 mg, 48%) as white powder.

Workup

  1. temperaturewhile cooling in an ice bath
  2. customThe solvent was evaporated
  3. customto give a residue, which
  4. customat room temperature
  5. stirringby stirring for 2 hr
  6. customThe reaction mixture was partitioned between ethyl acetate
  7. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate and brine in this order
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated
  10. customto give a residue, which
  11. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=95:5)
  12. additionFractions containing the target compound
  13. concentrationwere concentrated under a reduced pressure
  14. customto give a residue, which
  15. customwas dried in vacuum

Sources & evidence

ORD record
ord-a4c87acef4c14864a31ec941e9464b2d
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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