Boron trifluoride etherate → 2-[4-[[2-(5-Chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]phenyl]-3-hydroxy-cyclopent-2-en-1-one

HRID 1509052Notes

Reaction equation

HRID 1509052 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=3)[C:10]([CH2:22][CH3:23])=[C:9]([CH3:24])[N:8]=2)=[CH:4][CH:3]=1.C[Si](C)(C)[O:27][C:28]1[CH2:31][CH2:30][C:29]=1[O:32][Si](C)(C)C.B(F)(F)F.CCOCC.C(=O)(O)[O-].[Na+]>ClCCl>[Cl:1][C:2]1[S:6][C:5]([C:7]2[N:12]=[C:11]([NH:13][C:14]3[CH:21]=[CH:20][C:17]([C:18]4[C:28](=[O:27])[CH2:31][CH2:30][C:29]=4[OH:32])=[CH:16][CH:15]=3)[C:10]([CH2:22][CH3:23])=[C:9]([CH3:24])[N:8]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 516892Sodium BicarbonateHCID 27340341,2-Bis(trimethylsiloxy)cyclobuteneHCID 901115134-[[2-(5-Chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]benzaldehyde

Product 1

HCID 742205782-[4-[[2-(5-Chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]phenyl]-3-hydroxy-cyclopent-2-en-1-oneYield 13.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 18-mL vial was charged with 4-[[2-(5-Chloro-2-thienyl)-5-ethyl-6-methyl-pyrimidin-4-yl]amino]benzaldehyde (139 mg, 0.39 mmol, 1 eq.), trimethyl-(2-trimethylsilyloxycyclobuten-1-yl)oxy-silane (140 mg, 0.6 mmol, 1.53 eq.), and dichloromethane (2 ml). To the mixture was added BF3/Et2O (80 μL, 0.63 mmol, 1.6 eq.). The mixture was stirred at room temperature overnight and then added to sodium bicarbonate solution (10 ml). The mixture was extracted with ethyl acetate (3×5 ml). The organic layers were combined and dried over Na2SO4. Removal of solvent gave a residue, which was purified by chromatography on silica gel using 2˜3% of methanol in dichloromethane as eluent to give the title compound as a solid (22 mg, 13% yield). MW=425.93. 1H NMR (400 MHz, DMSO-d6) δ 12.4 (brs, 1H), 8.52 (brs, 1H), 7.92 (d, J=8.8 Hz, 2H), 7.67 (d, J=8.8 Hz, 2H), 7.56 (d, J=4.0 Hz, 1H), 7.15 (d, J=4.0 Hz, 1H), 3.34 (m, 4H), 2.73 (q, J=7.2 Hz, 2H), 2.40 (s, 3H), 1.11 (t, J=7.2 Hz, 3H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (3×5 ml)
  2. dry with materialdried over Na2SO4
  3. customRemoval of solvent
  4. customgave a residue, which
  5. customwas purified by chromatography on silica gel using 2˜3% of methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-8eac3748d3864e9bbecc3a49fb2639d6
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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