4-chloro-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine → HCID 67385657, compound

HRID 912138Notes

Reaction equation

HRID 912138 reaction equation
C([Li])CCC.C([Mg]Cl)(C)C.Br[C:12]1[N:17]=[CH:16][C:15]([N:18]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[CH:14][CH:13]=1.Cl[C:38]1[C:39]2[CH2:52][CH2:51][N:50]([C:53]3[CH:58]=[CH:57][N:56]=[CH:55][CH:54]=3)[C:40]=2[N:41]=[C:42]([N:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)[N:43]=1>O1CCCC1.[Cl-].[Zn+2].[Cl-].O>[CH3:27][O:26][C:23]1[CH:24]=[CH:25][C:20]([CH2:19][N:18]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[C:15]2[CH:16]=[N:17][C:12]([C:38]3[C:39]4[CH2:52][CH2:51][N:50]([C:53]5[CH:54]=[CH:55][N:56]=[CH:57][CH:58]=5)[C:40]=4[N:41]=[C:42]([N:44]4[CH2:45][CH2:46][O:47][CH2:48][CH2:49]4)[N:43]=3)=[CH:13][CH:14]=2)=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 592447084-chloro-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidineHCID 86640120HCID 86640120, compoundHCID 178418339ButyllithiumHCID 178418918HCID 178418918, compound

Product 1

HCID 67385657HCID 67385657, compoundYield 7.1%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of n-butyl lithium (1.56M hexane solution, 0.23 ml, 0.363 mmol) in tetrahydrofuran (2 ml), at 0° C., isopropyl magnesium chloride (2M tetrahydrofuran solution, 0.09 ml, 0.182 mmol) was added, followed by stirring for 15 minutes. To this, a solution of (6-bromo-pyridin-3-yl)-bis-(4-methoxy-benzyl)-amine (50 mg, 0.121 mmol, 1.0 equivalent) in tetrahydrofuran (1 ml) was added, followed by stirring for 1.5 hours. Zinc chloride (1M diethyl ether solution, 0.55 ml, 0.545 mmol) was added, and the temperature was raised to room temperature, followed by stirring for 1 hour. 4-Chloro-2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine (38.4 mg, 0.121 mmol) was added, followed by refluxing for 2 hours. Water was added, followed by extraction with ethyl acetate, and the organic layer was washed with brine. After drying over sodium sulfate, concentration was carried out under reduced pressure. Purification by preparative TLC (dichloromethane/methanol=40/1) afforded bis-(4-methoxy-benzyl)-[6-(2-morpholin-4-yl-7-pyridin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyridin-3-yl]-amine (5.3 mg, yield 7%).

Workup

  1. stirringby stirring for 1.5 hours
  2. stirringby stirring for 1 hour
  3. temperatureby refluxing for 2 hours
  4. extractionfollowed by extraction with ethyl acetate
  5. washthe organic layer was washed with brine
  6. dry with materialAfter drying over sodium sulfate, concentration
  7. customPurification by preparative TLC (dichloromethane/methanol=40/1)

Sources & evidence

ORD record
ord-be4341fbab6e4b5f843137cc16ad4ed3
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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