Diethyl Ether → HCID 57677338, compound

HRID 492800Notes

Reaction equation

HRID 492800 reaction equation
[NH2:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][C:7]2[N: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.CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.[C:43]1([CH2:49][C:50]([N:52]=[C:53]=[S:54])=[O:51])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(OCC)C>C(O)C.CCCCCC>[F:27][C:4]1[CH:3]=[C:2]([NH:1][C:53]([NH:52][C:50](=[O:51])[CH2:49][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)=[S:54])[CH:26]=[CH:25][C:5]=1[O:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:24])[N:15]([CH3:23])[CH:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)[CH:8]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 12454157Phenylacetyl isothiocyanateHCID 23153183HCID 23153183, compound

Product 1

HCID 57677338HCID 57677338, compoundYield 16.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8058HexaneSolvent

Procedure

3-[6-(4-Amino-2-fluorophenoxy)pyrimidin-4-yl}-1-methyl-1-(1-methylpiperidin-4-yl)urea (50 mg) was dissolved in ethanol (1 ml), and then D-10-camphorsulfonic acid (62.3 mg) was added thereto, followed by stirring for 5 min. Phenylacetyl isothiocyanate (toluene solution, 0.355 M, 0.565 ml) was added thereto, followed by stirring further for 1 hr. The reaction mixture was partitioned between ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) 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). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (0.5 ml)-hexane (2.0 ml) was then added to suspend a solid. The solid was filtered off and dried under aeration to provide the titled compound (12.4 mg, 16.8%) as pale yellow powder.

Workup

  1. stirringby stirring further for 1 hr
  2. customThe reaction mixture was partitioned between ethyl acetate (30 ml)
  3. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) in this order
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated
  6. customto give a residue, which
  7. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate)
  8. additionFractions containing the target compound
  9. concentrationwere concentrated
  10. customto give a residue
  11. filtrationThe solid was filtered off
  12. customdried under aeration

Sources & evidence

ORD record
ord-adfb0feb338c4f5a8228ed98068e09b6
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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