1-Methylpiperazine → HCID 68525679, compound

HRID 1036378Notes

Reaction equation

HRID 1036378 reaction equation
CS([C:5]1[C:14]2[CH2:13][CH2:12][C:11]3[O:15][CH:16]=[CH:17][C:10]=3[C:9]=2[N:8]=[C:7]([NH2:18])[N:6]=1)(=O)=O.[CH3:19][N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>COCCO>[CH3:19][N:20]1[CH2:25][CH2:24][N:23]([C:5]2[C:14]3[CH2:13][CH2:12][C:11]4[O:15][CH:16]=[CH:17][C:10]=4[C:9]=3[N:8]=[C:7]([NH2:18])[N:6]=2)[CH2:22][CH2:21]1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 68524387HCID 68524387, compound

Product 1

HCID 68525679HCID 68525679, compound

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
110 °C

Procedure

The product from Example 19A (26 mg, 0.11 mmol) was dissolved in dichloromethane (2 mL), treated with 70% 3-chloroperoxybenzoic acid (83 mg, 0.34 mmol), stirred at room temperature for 1 hour, treated with sodium sulfite solution, treated with sodium bicarbonate solution, and extracted with dichloromethane (2×). The combined dichloromethane layers were dried (magnesium sulfate), filtered, concentrated and chromatographed using ethyl acetate in dichloromethane to provide the sulfone intermediate, 4-(methylsulfonyl)-5,6-dihydrofuro[2,3-h]quinazolin-2-amine. This sulfone intermediate was treated with excess 1-methylpiperazine (110 mg, 1.1 mmol) in 2-methoxyethanol (1 mL) heated to 110° C. over night. The reaction mixture was cooled and partitioned between 1 M sodium hydroxide and dichloromethane. The layers were separated and the aqueous layer was extracted with dichloromethane (2×). The combined dichloromethane layers were dried (magnesium sulfate), filtered, concentrated and chromatographed (2, 3.5 and 5% (9:1 methanol:concentrated ammonium hydroxide) in dichloromethane) to provide the title compound: 1H NMR (300 MHz, CDCl3) δ 2.36 (s, 3H), 2.55 (t, J=4.7 Hz, 4H), 2.81 (m, 2H), 2.93 (m, 2H), 3.33 (t, J=4.7 Hz, 4H), 4.80 (br s, 2H), 7.13 (d, J=5.1 Hz, 1H), 7.53 (d, J=5.1 Hz, 1H); MS (DCI/NH3) m/z 286 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between 1 M sodium hydroxide and dichloromethane
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with dichloromethane (2×)
  5. dry with materialThe combined dichloromethane layers were dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed (2, 3.5 and 5% (9:1 methanol:concentrated ammonium hydroxide) in dichloromethane)

Sources & evidence

ORD record
ord-ae2afb34892f4f47bac961cd1cfe6eef
Source dataset
uspto-grants-2013_10
Patent number
US08546410B2

Reaction notes

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