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Hexane → 1-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-{6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}-1-methylurea

HRID 492963
Notes
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Reaction equation

HRID 492963 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]([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@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[C:47]1([CH2:53][C:54]([N:56]=[C:57]=[S:58])=[O:55])[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.CCCCCC>C(O)C.C1(C)C=CC=CC=1.C(OCC)C>[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:57]([NH:56][C:54](=[O:55])[CH2:53][C:47]4[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=4)=[S:58])=[CH:3][C:4]=3[F:31])[N:12]=[CH:11][N:10]=2)=[O:28])[CH2:18][CH2:19]1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 8058HexaneHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 12454157Phenylacetyl isothiocyanateHCID 231530283-[6-(4-Amino-2-fluorophenoxy)pyrimidin-4-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea

Product 1

HCID 576774581-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-{6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}-1-methylurea
Yield 16.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (110 mg) in ethanol (2.0 ml) was added (1S)-(+)-10-camphorsulfonic acid (101 mg), followed by stirring at room temperature for 15 min. A solution of 2-phenylacetyl isothiocyanate in toluene (0.25 M, 3.06 ml) was added to the reaction mixture, followed by stirring at room temperature for 2 hrs. The reaction mixture was partitioned between ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (10 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, ethyl acetate:methanol=20:1, then 10:1). Fractions containing a target compound were concentrated to give a solid, which was suspended in diethyl ether:hexane=1:1. The solid was filtered off, and washed with diethyl ether to provide the titled compound (25.3 mg, 16.3%) as pale yellow powder.

Workup

  1. stirringby stirring at room temperature for 2 hrs
  2. customThe reaction mixture was partitioned between ethyl acetate (30 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 a target compound
  9. concentrationwere concentrated
  10. customto give a solid, which
  11. filtrationThe solid was filtered off
  12. washwashed with diethyl ether

Sources & evidence

ORD record
ord-3f3c73a4c1d84057a26dc07a37c7600b
Source dataset
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07531532B2

Reaction notes

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