Diethyl Ether → HCID 23153637, compound

HRID 492811Notes

Reaction equation

HRID 492811 reaction equation
[NH2:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:24])[N:15]([CH3:23])[CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)[CH:8]=2)=[C:4]([F:27])[CH:3]=1.[C:28]1([CH2:34][C:35]([N:37]=[C:38]=[O:39])=[O:36])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(OCC)C.CCCCCC>O1CCCC1.FC1C=C(NC(NC(=O)CC2C=CC=CC=2)=S)C=CC=1OC1N=CN=C(NC(N2CCCC2)=O)C=1>[F:27][C:4]1[CH:3]=[C:2]([NH:1][C:38]([NH:37][C:35](=[O:36])[CH2:34][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:39])[CH:26]=[CH:25][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:24])[N:15]([CH3:23])[CH:16]2[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]2)[CH:8]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 8058HexaneHCID 12259960Phenylacetyl isocyanateHCID 231535663-[4-(4-Amino-2-fluorophenoxy)pyridin-2-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea

Product 1

HCID 23153637HCID 23153637, compoundYield 88.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 11248939Pyrrolidine-1-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}amideSolvent

Procedure

3-[4-(4-Amino-2-fluorophenoxy)pyridin-2-yl]-1-methyl-1-(1-methylpiperidin-4-yl)urea (50.0 mg) was dissolved in tetrahydrofuran (2 ml) under a nitrogen atmosphere, and then a solution of phenylacetyl isocyanate in toluene (0.80 ml, 0.5 M solution in toluene, Production Example 1) was added thereto, followed by stirring for 1 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, water 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:ethanol=9:1) Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (1 ml)-hexane (0,5 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (63.1 mg, 88.1%) as a pale yellow solid.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:ethanol=9:1) Fractions
  7. additioncontaining the target compound
  8. concentrationwere concentrated
  9. customto give a residue
  10. filtrationThe solid was filtered off
  11. customdried under aeration

Sources & evidence

ORD record
ord-4833f50fa85a48fc919e66dfbef412a8
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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