Sodium hydride → 4-(3-Methoxy-phenyl)-7-[2-(4-methyl-piperazin-1-yl)-pyridin-4-yl]-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine

HRID 912098Notes

Reaction equation

HRID 912098 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:15]=[C:14]([NH2:16])[CH:13]=[CH:12][N:11]=2)[CH2:6][CH2:5]1.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]([N:7]5[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]5)[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 592449894-(3-Methoxy-phenyl)-7-[2-(4-methyl-piperazin-1-yl)-pyridin-4-yl]-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidineYield 81.3%

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, and the resulting mixture was heated to reflux 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 16 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 (107 mg).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 2 hours
  3. temperatureby heating
  4. temperatureto reflux for 16 hours
  5. temperatureThe reaction mixture was cooled
  6. additionwhich was subsequently added dropwise slowly onto ice water
  7. extractionfollowed by extraction twice with ethyl acetate (10 ml)
  8. washThe organic layer was washed with brine (10 ml)
  9. dry with materialdried over sodium sulfate
  10. distillationby distilling off under reduced pressure

Sources & evidence

ORD record
ord-1d604ae51cd1486ebf0fe432245a6083
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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