Diethyl Ether → HCID 57677614, compound

HRID 492937Notes

Reaction equation

HRID 492937 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:28])[N:15]([CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])[CH2:19][CH2:18]3)[CH3:16])[CH:8]=2)=[C:4]([F:31])[CH:3]=1.[C:32]1([CH2:38][C:39]([N:41]=[C:42]=[O:43])=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(OCC)C>O1CCCC1.CCCCCC>[CH3:26][N:25]([CH3:27])[CH2:24][CH2:23][N:20]1[CH2:21][CH2:22][CH:17]([N:15]([CH3:16])[C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:29]=[CH:30][C:2]([NH:1][C:42]([NH:41][C:39](=[O:40])[CH2:38][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:43])=[CH:3][C:4]=3[F:31])[CH:12]=[CH:11][N:10]=2)=[O:28])[CH2:18][CH2:19]1

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 12259960Phenylacetyl isocyanateHCID 23152965HCID 23152965, compound

Product 1

HCID 57677614HCID 57677614, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×

Procedure

To a solution of 3-[4-(4-amino-2-fluorophenoxy)pyridin-2-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (61 mg) in tetrahydrofuran (3.0 ml) was added a solution of 2-phenylacetyl isocyanate in hexane (0.2 M, 1.70 ml) at room temperature, followed by stirring at room temperature for 9.5 hrs. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=10:1). Fractions containing a target compound were concentrated to give a residue, to which diethyl ether (1 ml) and hexane (1 ml) were added to give a precipitate. The precipitate was filtered off, and dried under aeration to provide the titled compound (17.8 mg, 21%) as white powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationThe organic layer was concentrated
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent
  8. additionFractions containing a target compound
  9. concentrationwere concentrated
  10. customto give a residue
  11. customto give a precipitate
  12. filtrationThe precipitate was filtered off
  13. customdried under aeration

Sources & evidence

ORD record
ord-cdfd1984ecb24f5c9878e9d2cc28240f
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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