Hexane → Pyrrolidine-1-carboxylic acid [6-(2-fluoro-4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyrimidin-4-yl]amide

HRID 492767Notes

Reaction equation

HRID 492767 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](Cl)=[O:10])=[CH:4][CH:3]=1.[S-:12][C:13]#[N:14].[K+].[NH2:16][C:17]1[CH:37]=[CH:36][C:20]([O:21][C:22]2[CH:27]=[C:26]([NH:28][C:29]([N:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[O:30])[N:25]=[CH:24][N:23]=2)=[C:19]([F:38])[CH:18]=1.CCCCCC>C(#N)C.C(OCC)C>[F:38][C:19]1[CH:18]=[C:17]([NH:16][C:13]([NH:14][C:9](=[O:10])[CH2:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[S:12])[CH:37]=[CH:36][C:20]=1[O:21][C:22]1[N:23]=[CH:24][N:25]=[C:26]([NH:28][C:29]([N:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)=[O:30])[CH:27]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 516872Potassium thiocyanateHCID 37449884-Fluorophenylacetyl chlorideHCID 231534594-(4-Amino-2-fluorophenoxy)-6-[(pyrrolidin-1-yl)carbonylamino]pyrimidine

Product 1

HCID 57677439Pyrrolidine-1-carboxylic acid [6-(2-fluoro-4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyrimidin-4-yl]amideYield 69.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent2×

Procedure

2-(4-Fluorophenyl)acetyl chloride (135 mg) was dissolved in acetonitrile (5 ml) under a nitrogen atmosphere, and then potassium thiocyanate (152 mg) was added thereto at 60° C., followed by stirring at the same temperature for 1.5 hrs. The reaction mixture was cooled down to room temperature, and then a solution of 4-(4-amino-2-fluorophenoxy)-6-[(pyrrolidin-1-yl) carbonylamino]pyrimidine (99.6 mg) in acetonitrile (3 ml) was added thereto, followed by stirring for 15 min. 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 under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3). Fractions containing the target compound were concentrated to give a residue, which was suspended in diethyl ether (5 ml)-hexane (5 ml). The solid was filtered off and dried under aeration to provide the titled compound (111.8 mg, 69.5%) as a pale yellow solid.

Workup

  1. customat 60° C.
  2. stirringby stirring for 15 min
  3. customThe reaction mixture was partitioned between ethyl acetate
  4. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under a reduced pressure
  7. customto give a residue, which
  8. customwas then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:3)
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. customto give a residue, which
  12. filtrationThe solid was filtered off
  13. customdried under aeration

Sources & evidence

ORD record
ord-c5584f1588644cf594bbffaac0ef1f18
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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