(1S)-(+)-Camphor-10-sulphonic acid → HCID 57677631, compound

HRID 492904Notes

Reaction equation

HRID 492904 reaction equation
[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[NH2:16][C:17]1[CH:45]=[CH:44][C:20]([O:21][C:22]2[N:27]=[CH:26][N:25]=[C:24]([NH:28][C:29](=[O:43])[N:30]([CH:32]3[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][N:40]([CH3:42])[CH3:41])[CH2:34][CH2:33]3)[CH3:31])[CH:23]=2)=[CH:19][CH:18]=1.[F:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:53][C:54]([N:56]=[C:57]=[S:58])=[O:55])=[CH:49][CH:48]=1>C(O)C>[CH3:42][N:40]([CH3:41])[CH2:39][CH2:38][N:35]1[CH2:36][CH2:37][CH:32]([N:30]([CH3:31])[C:29]([NH:28][C:24]2[CH:23]=[C:22]([O:21][C:20]3[CH:44]=[CH:45][C:17]([NH:16][C:57]([NH:56][C:54](=[O:55])[CH2:53][C:50]4[CH:51]=[CH:52][C:47]([F:46])=[CH:48][CH:49]=4)=[S:58])=[CH:18][CH:19]=3)[N:27]=[CH:26][N:25]=2)=[O:43])[CH2:33][CH2:34]1

Participants

5

Reactant 3

HCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 23153319HCID 23153319, compound

Product 1

HCID 57677631HCID 57677631, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

After adding (1S)-(+)-10-camphorsulfonic acid (127 mg) to a solution of crude 3-[6-(4-aminophenoxy)pyrimidin-4-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (119 mg) in ethanol (3.0 ml), the mixture was stirred for 15 minutes at room temperature. After then adding 2-(4-fluorophenyl)acetyl isothiocyanate (4.08 ml, 0.25 M solution in toluene) thereto, the mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between saturated aqueous sodium hydrogencarbonate (10 ml) and ethyl acetate (30 ml). The organic layer was washed with brine and dried over anhydrous sodium sulfate. The dried organic layer was concentrated and the residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the target compound were concentrated, and the residue was purified by LC-MS (water-acetonitrile-trifluoroacetic acid system). Fractions containing the target compound were concentrated, saturated aqueous sodium hydrogencarbonate was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was then dried over anhydrous sodium sulfate. The dried organic layer was concentrated. Diethyl ether was added to the obtained solid to produce a suspension. The resulting precipitate was filtered and then dried to provide the title compound (12.4 mg) as white powder.

Workup

  1. customThe reaction mixture was partitioned between saturated aqueous sodium hydrogencarbonate (10 ml) and ethyl acetate (30 ml)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe dried organic layer was concentrated
  5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  6. additionFractions containing the target compound
  7. concentrationwere concentrated
  8. customthe residue was purified by LC-MS (water-acetonitrile-trifluoroacetic acid system)
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. additionsaturated aqueous sodium hydrogencarbonate was added to the residue
  12. extractionthe mixture was extracted with ethyl acetate
  13. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  14. concentrationThe dried organic layer was concentrated
  15. additionDiethyl ether was added to the obtained solid
  16. customto produce a suspension
  17. filtrationThe resulting precipitate was filtered
  18. customdried

Sources & evidence

ORD record
ord-fc153f290c474f6b83ddea1ff026c9f7
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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