Diethyl Ether → HCID 23153522, compound

HRID 492996Notes

Reaction equation

HRID 492996 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:28])[N:15]([CH3:27])[CH:16]3[CH2:21][CH2:20][N:19]([CH:22]4[CH2:25][N:24]([CH3:26])[CH2:23]4)[CH2:18][CH2:17]3)[CH:8]=2)=[C:4]([F:31])[CH:3]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[F:47][C:48]1[CH:53]=[CH:52][C:51]([CH2:54][C:55]([N:57]=[C:58]=[S:59])=[O:56])=[CH:50][CH:49]=1.C(OCC)C>C(O)C.C1(C)C=CC=CC=1.CCCCCC>[F:31][C:4]1[CH:3]=[C:2]([NH:1][C:58]([NH:57][C:55](=[O:56])[CH2:54][C:51]2[CH:52]=[CH:53][C:48]([F:47])=[CH:49][CH:50]=2)=[S:59])[CH:30]=[CH:29][C:5]=1[O:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:28])[N:15]([CH3:27])[CH:16]2[CH2:17][CH2:18][N:19]([CH:22]3[CH2:23][N:24]([CH3:26])[CH2:25]3)[CH2:20][CH2:21]2)[CH:8]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 23153442HCID 23153442, compound

Product 1

HCID 23153522HCID 23153522, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8058HexaneSolvent

Procedure

To a solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1-methyl-1-[1-(1-methylazetidin-3-yl)piperidin-4-yl]urea (68.0 mg) in ethanol (2.0 ml) was added (1S)-(+)-10-camphorsulfonic acid (70.2 mg), followed by stirring at room temperature for 10 min. A solution of 2-(4-fluorophenyl)acetyl isothiocyanate in toluene (0.25 M, 1.91 ml) was added to the reaction mixture, followed by stirring at room temperature for 30 min. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The 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=25:1). Fractions containing the target compound were concentrated to give a residue, to which were added diethyl ether (2 ml) and hexane (2 ml) to give a precipitate. The precipitate was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (10.9 mg, 11.0%) as white powder.

Workup

  1. stirringby stirring at room temperature for 30 min
  2. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  3. washThe 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 the target compound
  9. concentrationwere concentrated
  10. customto give a residue
  11. customto give a precipitate
  12. filtrationThe precipitate was filtered off
  13. washwashed with diethyl ether
  14. customdried under aeration

Sources & evidence

ORD record
ord-73463095be1843b9961d13de13ae0f1d
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…