Sodium hydride → HCID 59628445, compound

HRID 912145Notes

Reaction equation

HRID 912145 reaction equation
[CH3:1][O:2][C:3]1[CH:40]=[CH:39][C:6]([CH2:7][N:8]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[C:9]2[N:14]=[CH:13][C:12]([C:15]3[C:16]4[CH2:29][CH2:28][NH:27][C:17]=4[N:18]=[C:19]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:20]=3)=[CH:11][N:10]=2)=[CH:5][CH:4]=1.[H-].[Na+].[S:43](Cl)([CH3:46])(=[O:45])=[O:44].[Cl-].[NH4+]>O1CCCC1>[CH3:46][S:43]([N:27]1[C:17]2[N:18]=[C:19]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[N:20]=[C:15]([C:12]3[CH:11]=[N:10][C:9]([N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:40][CH:39]=4)[CH2:30][C:31]4[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=4)=[N:14][CH:13]=3)[C:16]=2[CH2:29][CH2:28]1)(=[O:45])=[O:44]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 45258862Bis-(4-methoxybenzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine

Product 1

HCID 59628445HCID 59628445, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To tetrahydrofuran solution (2 ml) of bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (100 mg, 0.185 mmol), 60% sodium hydride (222 mg, 5.56 mmol) was added, followed by stirring at room temperature for 30 minutes. To this, mesyl chloride (430 μl, 5.56 mmol) was added, followed by refluxing for 6 hours. This was cooled to room temperature, followed by addition of saturated aqueous ammonium chloride solution, and passed through Whatman tube. The resulting organic phase was concentrated under reduced pressure, followed by purification by silica gel column chromatography (dichloromethane/methanol=200/1), to obtain [5-(7-methanesulfonyl-2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-bis-(4-methoxy-benzyl)-amine (80.2 mg, Yield 70%). To this, trifluoroacetic acid (1 ml) and concentrated sulfuric acid (2 drops) were added, followed by stirring at 40° C. for 3 hours. After concentration of trifluoroacetic acid under reduced pressure, water was added, followed by neutralization with 1M aqueous sodium hydroxide solution. The solid was filtered, followed by purification by silica gel column chromatography (dichloromethane/2M ammonia methanol=30/1), to obtain the desired compound as a yellow solid (14.9 mg, Yield 31%).

Workup

  1. temperatureby refluxing for 6 hours
  2. temperatureThis was cooled to room temperature
  3. concentrationThe resulting organic phase was concentrated under reduced pressure
  4. customfollowed by purification by silica gel column chromatography (dichloromethane/methanol=200/1)

Sources & evidence

ORD record
ord-9d28a3a9e40e4df18b09aaef2e900c34
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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