Methylamine → HCID 67280840, compound

HRID 1693289Notes

Reaction equation

HRID 1693289 reaction equation
OC1[C:11]2[CH2:10][S:9][N:8]=[C:7]([N:12](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[C:6]3=[N:27][N:28]([CH2:30][C:31]4[C:36]([CH3:37])=[C:35]([O:38][CH3:39])[C:34]([CH3:40])=[CH:33][N:32]=4)[N:29]=[C:4]([C:5]=23)[CH2:3]1.ClCCl.ClC(Cl)(O[C:48](=[O:54])[O:49][C:50](Cl)(Cl)Cl)Cl.[CH3:56][NH2:57]>O1CCCC1.N1C=CC=CC=1>[CH3:56][NH:57][C:48](=[O:54])[O:49][CH:50]1[C:11]2[CH2:10][S:9][N:8]=[C:7]([NH2:12])[C:6]3=[N:27][N:28]([CH2:30][C:31]4[C:36]([CH3:37])=[C:35]([O:38][CH3:39])[C:34]([CH3:40])=[CH:33][N:32]=4)[N:29]=[C:4]([C:5]=23)[CH2:3]1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 6344DichloromethaneHCID 94429TriphosgeneHCID 86641323HCID 86641323, compound

Product 1

HCID 67280840HCID 67280840, compoundYield 22%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture composed of di-tert-butyl {8-hydroxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-2,7,8,9-tetrahydro-6-thia-1,2,3,5-tetraazabenzo[cd]azulen-4-yl}imidodicarbonate of Example 32 (40 mg), dehydrated dichloromethane (1 mL), pyridine (11 μL) and triphosgene (8.7 mg) was stirred under cooling in an ice bath for three hours. A 2 N solution of methylamine in tetrahydrofuran (0.6 mL) was added to the reaction mixture. Then, the ice bath was removed and the mixture was stirred for 17 hours. After confirming that the raw material disappeared, the reaction mixture was diluted with chloroform and washed with water. The aqueous layer was extracted with chloroform, and then the combined organic layers were dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. Dichloromethane (2 mL) and trifluoroacetic acid (0.5 mL) were added to the resulting residue, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by reversed phase liquid chromatography to obtain the title compound (6.6 mg, 22%) as a solid.

Workup

  1. temperatureunder cooling in an ice bath for three hours
  2. customThen, the ice bath was removed
  3. stirringthe mixture was stirred for 17 hours
  4. additionthe reaction mixture was diluted with chloroform
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with chloroform
  7. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  8. filtrationAfter filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. additionDichloromethane (2 mL) and trifluoroacetic acid (0.5 mL) were added to the resulting residue
  11. stirringthe mixture was stirred at room temperature for 15 hours
  12. concentrationThe reaction mixture was concentrated under reduced pressure
  13. customthe resulting residue was purified by reversed phase liquid chromatography

Sources & evidence

ORD record
ord-fe118cbf7b054ca99d9b051039fffe3a
Source dataset
uspto-grants-2012_04
Patent number
US08158638B2

Reaction notes

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