Sodium hydride → (2-{4-[4-(3-Methoxy-phenyl)-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl]-pyridin-2-yloxy}-ethyl)-dimethyl-amine

HRID 912101Notes

Reaction equation

HRID 912101 reaction equation
[H-].[Na+].CN1CCN([C:10]2[CH:15]=[C:14]([NH2:16])[CH:13]=[CH:12][N:11]=2)CC1.Cl[C:18]1[C:23]([CH2:24][CH2:25]Cl)=[C:22]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=2)[N:21]=[C:20]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[N:19]=1>O1CCCC1>[CH3:34][O:33][C:29]1[CH:28]=[C:27]([C:22]2[C:23]3[CH2:24][CH2:25][N:16]([C:14]4[CH:13]=[CH:12][N:11]=[C:10]([O:38][CH2:37][CH2:36][N:35]([CH3:40])[CH3:20])[CH:15]=4)[C:18]=3[N:19]=[C:20]([N:35]3[CH2:40][CH2:39][O:38][CH2:37][CH2:36]3)[N:21]=2)[CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118391892-(4-Methylpiperazin-1-yl)pyridin-4-amineHCID 592449884-[4-Chloro-5-(2-chloroethyl)-6-(3-methoxyphenyl)-pyrimidin-2-yl]morpholine

Product 1

HCID 59244652(2-{4-[4-(3-Methoxy-phenyl)-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidin-7-yl]-pyridin-2-yloxy}-ethyl)-dimethyl-amineYield 320.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (108 mg, 60% mineral oil dispersion, 2.72 mmol) was placed in a dried flask under a nitrogen atmosphere, followed by sequential addition of anhydrous tetrahydrofuran (10 ml) and 2-(4-methylpiperazin-1-yl)pyridin-4-ylamine (62 mg, 0.32 mmol) with a syringe. After the resulting mixture was stirred at room temperature for 2 hours, 4-[4-chloro-5-(2-chloroethyl)-6-(3-methoxyphenyl)-pyrimidin-2-yl]morpholine (100 mg, 0.27 mmol) was added, followed by heating to reflux for 4 hours. The reaction mixture was cooled, which was subsequently added dropwise slowly onto ice water, followed by extraction twice with ethyl acetate (10 ml). The organic layer was washed with brine (10 ml), and dried over sodium sulfate, followed by distilling off under reduced pressure, to obtain a crude product as a red oil (206 mg).

Workup

  1. temperatureby heating
  2. temperatureto reflux for 4 hours
  3. temperatureThe reaction mixture was cooled
  4. additionwhich was subsequently added dropwise slowly onto ice water
  5. extractionfollowed by extraction twice with ethyl acetate (10 ml)
  6. washThe organic layer was washed with brine (10 ml)
  7. dry with materialdried over sodium sulfate
  8. distillationby distilling off under reduced pressure

Sources & evidence

ORD record
ord-0ac4a423a08a47b1b67320a2ab0cc7f4
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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