Sodium hydride → Ether isohexane

HRID 1767748Notes

Reaction equation

HRID 1767748 reaction equation
[H-].[Na+].Cl[C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH2:17][CH2:18]CN3CCOCC3)=C(OC)[CH:12]=2)N=CN=1>O1CCCC1.ClCCl.CO>[CH3:10][CH2:9][CH2:8][CH:13]([CH3:4])[CH3:12].[CH3:9][CH2:10][O:16][CH2:17][CH3:18]

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21882825Ether isohexaneYield 353.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
70 °C

Procedure

Sodium hydride (500 mg of a 60% suspension in mineral oil, 10 mmol) was added to a solution of with 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (2.02 g, 6.0 mmol) 2-diethyoxymethyl-5-aminopyrimidine (1.0 g, 5.0 mmol) in tetrahydrofuran (25 ml) and the reaction was heated at 70° C. for 2 hours. The reaction was cooled and excess sodium hydride quenched by the addition of methanol (1 ml) followed by concentration to dryness. The residue was dissolved in dichloromethane/methanol 20:1 (30 ml) and poured quickly through silica gel (20 g in a sinter funnel). Elution with dichloromethane/methanol 20:1 yielded 4-(2-diethoxymethyl-5-aminopyrimidine)-6-methoxy-7-(3-morpholinopropoxy)quinazoline after trituration with isohexane/ether (1:1) as an off-white solid (1.7 g, 70% yield):

Workup

  1. temperatureThe reaction was cooled
  2. customexcess sodium hydride quenched by the addition of methanol (1 ml)
  3. concentrationfollowed by concentration to dryness
  4. dissolutionThe residue was dissolved in dichloromethane/methanol 20:1 (30 ml)
  5. additionpoured quickly through silica gel (20 g in a sinter funnel)

Sources & evidence

ORD record
ord-df1fc44385234f9398dbd03b1f469f71
Source dataset
uspto-grants-2007_06
Patent number
US07235559B1

Reaction notes

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