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Methyl iodide → 2-[N-Methyl-(5,6,6a,7,8,9-hexahydro-6a-methyl-4H-2-phenalenyl)amino]pyrimidine-5-carboxylic acid

HRID 1097401
Notes
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Reaction equation

HRID 1097401 reaction equation
[H-].[Na+].[CH3:3][C:4]12[C:16]3[C:8](=[CH:9][C:10]([NH:17][C:18]4[N:23]=[CH:22][C:21]([C:24]([O:26]CC)=[O:25])=[CH:20][N:19]=4)=[CH:11][C:12]=3[CH2:13][CH2:14][CH2:15]1)[CH2:7][CH2:6][CH2:5]2.I[CH3:30].[Cl-].[NH4+]>CN(C)C=O>[CH3:30][N:17]([C:10]1[CH:11]=[C:12]2[C:16]3[C:4]([CH3:3])([CH2:15][CH2:14][CH2:13]2)[CH2:5][CH2:6][CH2:7][C:8]=3[CH:9]=1)[C:18]1[N:23]=[CH:22][C:21]([C:24]([OH:26])=[O:25])=[CH:20][N:19]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 25190162HCID 25190162, compound

Product 1

HCID 251901602-[N-Methyl-(5,6,6a,7,8,9-hexahydro-6a-methyl-4H-2-phenalenyl)amino]pyrimidine-5-carboxylic acidYield 85%

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent
2×

Procedure

A suspension of sodium hydride (60%, 0.008 g) in N,N-dimethylformamide (2 ml) was added with ethyl 2-[(5,6,6a,7,8,9-hexahydro-6a-methyl-4H-2-phenalenyl)amino]pyrimidine-5-carboxylate (0.034 g) dissolved in N,N-dimethylformamide (1 ml), and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was added with iodomethane (0.018 ml), and the mixture was stirred overnight. The reaction mixture was added with saturated aqueous ammonium chloride, and the mixture was extracted with diethyl ether. The organic layer was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was suspended in ethanol (5 ml), the suspension was added with 20% aqueous sodium hydroxide (1 ml), and the mixture was stirred at 50° C. for 3 hours. The reaction mixture was left to cool and then made acidic with 2 N aqueous hydrochloric acid, and the mixture was extracted with chloroform. The organic layer was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was recrystallized from ethanol to obtain the title compound (0.028 g, yield: 85%) as colorless needles (melting point: >300° C.).

Workup

  1. stirringthe mixture was stirred overnight
  2. extractionthe mixture was extracted with diethyl ether
  3. washThe organic layer was washed successively with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. additionthe suspension was added with 20% aqueous sodium hydroxide (1 ml)
  7. stirringthe mixture was stirred at 50° C. for 3 hours
  8. waitThe reaction mixture was left
  9. temperatureto cool
  10. extractionthe mixture was extracted with chloroform
  11. washThe organic layer was washed successively with water and saturated brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationThe organic layer was concentrated under reduced pressure
  14. customthe resulting residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-9a1be2994b1941bd8bd11b6514ebaba7
Source dataset
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08143260B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes