Toluene → HCID 67385193, compound

HRID 912203Notes

Reaction equation

HRID 912203 reaction equation
C1(C)C=CC=CC=1.[CH3:8][N:9]([CH3:13])[CH2:10][CH2:11][OH:12].Cl[C:15]1[N:20]=[CH:19][C:18]([N:21]2[C:25]3[N:26]=[C:27]([N:55]4[CH2:60][CH2:59][O:58][CH2:57][CH2:56]4)[N:28]=[C:29]([C:30]4[CH:31]=[N:32][C:33]([N:36]([CH2:46][C:47]5[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=5)[CH2:37][C:38]5[CH:43]=[CH:42][C:41]([O:44][CH3:45])=[CH:40][CH:39]=5)=[N:34][CH:35]=4)[C:24]=3[CH2:23][CH2:22]2)=[CH:17][CH:16]=1.[H-].[Na+]>O>[CH3:8][N:9]([CH3:13])[CH2:10][CH2:11][O:12][C:15]1[N:20]=[CH:19][C:18]([N:21]2[C:25]3[N:26]=[C:27]([N:55]4[CH2:60][CH2:59][O:58][CH2:57][CH2:56]4)[N:28]=[C:29]([C:30]4[CH:31]=[N:32][C:33]([N:36]([CH2:46][C:47]5[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=5)[CH2:37][C:38]5[CH:39]=[CH:40][C:41]([O:44][CH3:45])=[CH:42][CH:43]=5)=[N:34][CH:35]=4)[C:24]=3[CH2:23][CH2:22]2)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 79022-(Dimethylamino)ethanolHCID 24758Sodium hydrideHCID 59244926HCID 59244926, compound

Product 1

HCID 67385193HCID 67385193, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a toluene solution (2 ml) of N,N-dimethylethanolamine (139 μl, 0.138 mmol) and {5-[7-(6-chloro-pyridin-3-yl)-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-pyrimidin-2-yl}-bis-(4-methoxy-benzyl)-amine (150 mg, 0.23 mmol) obtained in Step A in Example 1-D-48, 60% oily NaH (46 mg) was added, followed by refluxing for 4 hours. The reaction mixture was cooled to room temperature, and diluted with water, followed by extraction with ethyl acetate. The organic layer was dried over magnesium sulfate, followed by filtering off the magnesium sulfate, and subsequently the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane/methanol=50/1), to obtain a crude product of (5-{7-[6-(2-dimethylamino-ethoxy)-pyridin-3-yl]-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}-pyrimidin-2-yl)-bis-(4-methoxy-benzyl)-amine as a yellow solid (67 mg), and then the PMB groups were removed according to the above Deprotection method 2, to obtain the desired compound (D-72) as a yellow powder (12 mg, 29%).

Workup

  1. temperatureby refluxing for 4 hours
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationby filtering off the magnesium sulfate
  5. concentrationsubsequently the filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (dichloromethane/methanol=50/1)

Sources & evidence

ORD record
ord-de821cbe0ee74117a5258a8b3909c898
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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