Acetone → 4-tert-butyl-N-[6-{2-(5-(1-hydroxy-1-methylethyl)primidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide

HRID 2277

Reaction equation

HRID 2277 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][CH2:9][CH2:10][O:11][C:12]2[N:17]=[CH:16][N:15]=[C:14]([NH:18][S:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[C:13]=2[C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)=[N:6][CH:7]=1.C([Li])CCC.[CH3:44][C:45]([CH3:47])=[O:46].[Cl-].[NH4+]>CCCCCC.O1CCCC1>[C:28]([C:25]1[CH:26]=[CH:27][C:22]([S:19]([NH:18][C:14]2[C:13]([C:32]3[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=3)=[C:12]([O:11][CH2:10][CH2:9][O:8][C:5]3[N:4]=[CH:3][C:2]([C:45]([OH:46])([CH3:47])[CH3:44])=[CH:7][N:6]=3)[N:17]=[CH:16][N:15]=2)(=[O:21])=[O:20])=[CH:23][CH:24]=1)([CH3:31])([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 180AcetoneHCID 25517Ammonium ChlorideHCID 99385714-tert-butyl-N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamideHCID 178418339Butyllithium

Product 1

HCID 1317197564-tert-butyl-N-[6-{2-(5-(1-hydroxy-1-methylethyl)primidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamideYield 30.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of N-[6-{2-(5-bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (300 mg) in tetetrahydrofuran (10 ml) is added a 1.6M solution of n-butyl lithium in n-hexane (0.75 ml) at -78° C. The mixture is stirred at -78° C. for 5 minutes, and thereto is added a solution of acetone (58 mg) in tetrahydrofuran (1 ml), and the mixture is warmed to room temperature. The mixture is treated with aqueous ammonium chloride solution, and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=2:1~1:1), and recrystallized from ethyl acetate/n-hexane to give 4-tert-butyl-N-[6-{2-(5-(1-hydroxy-1-methylethyl)primidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide (88 mg) as crystals.

Workup

  1. temperaturethe mixture is warmed to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe ethyl acetate layer is washed
  4. customdried
  5. customevaporated
  6. customto remove the solvent
  7. customThe residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=2:1~1:1)
  8. customrecrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-962a8cae74e94e06a885467f87289f79
Source dataset
uspto-grants-1998_03
Patent number
US05728706

Linked notes

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