Sodium hydride → HCID 67385015, compound

HRID 912313Notes

Reaction equation

HRID 912313 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+].[Cl:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[N:50]=[C:51]=[O:52]>CN(C=O)C>[Cl:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[NH:50][C:51]([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:52]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 76833Chlorophenyl isocyanateHCID 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 67385015HCID 67385015, compoundYield 112.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a DMF solution (2 ml) of ice-cooled bis-(4-methoxy-benzyl)-[5-(2-morpholin-4-yl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl)-pyrimidin-2-yl]-amine (80.0 mg, 0.148 mmol), 60% oily NaH (18 mg) was added, followed by stirring at room temperature for 15 minutes. To the reaction mixture, 2-chlorophenylisocyanate (53.4 μl, 0.445 mmol) was added, followed by further stirring for 1 hour. The reaction mixture was ice-cooled, and quenched with water (1 ml). This was diluted with dichloromethane (10 ml), and washed with water (10 ml×2). After the organic layer was dried over sodium sulfate, the sodium sulfate was filtered off, and the filtrate was concentrated under reduced pressure, to obtain a crude product of 4-{2-[bis-(4-methoxy-benzyl)-amino]-pyrimidin-5-yl}-2-morpholin-4-yl-5,6-dihydro-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid (2-chloro-phenyl)-amide as a brown solid (115 mg), and then the PMB groups were removed according to the above Deprotection method 3, to obtain the desired compound (D-217) as a colorless powder (39.2 mg, 58%).

Workup

  1. additionwas added
  2. stirringby further stirring for 1 hour
  3. temperaturecooled
  4. customquenched with water (1 ml)
  5. additionThis was diluted with dichloromethane (10 ml)
  6. washwashed with water (10 ml×2)
  7. dry with materialAfter the organic layer was dried over sodium sulfate
  8. filtrationthe sodium sulfate was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-918af8d3134c430694bd3523281af279
Source dataset
uspto-grants-2011_09
Patent number
US08022205B2

Reaction notes

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