Methylamine → HCID 21993889, compound

HRID 1978420Notes

Reaction equation

HRID 1978420 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[C:15]([CH2:19][N:20]4C(=O)C5=CC=CC=C5C4=O)[CH:16]=3)[CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.NN.[N:34]1[CH:35]=[C:36]2[N:45]3[C:40](=[CH:41][CH:42]=[CH:43][C:44]=13)[S:39][C:38]([C:46]([OH:48])=O)=[CH:37]2.CN.P(C#N)(OCC)(OCC)=O.C(=O)([O-])O.[Na+]>C(O)C.CN(C)C=O.C(N(CC)CC)C>[C:1]1([CH2:7][CH2:8][CH2:9][N:10]2[CH2:18][C:17]3[C:12](=[CH:13][CH:14]=[C:15]([CH2:19][NH:20][C:46]([C:38]4[S:39][C:40]5[N:45]6[C:36](=[CH:35][N:34]=[C:44]6[CH:43]=[CH:42][CH:41]=5)[CH:37]=4)=[O:48])[CH:16]=3)[CH2:11]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

10

Reactant 6

HCID 6329MethylamineHCID 24654Hydrazine hydrate (1:1)HCID 76257Diethyl cyanophosphonateHCID 516892Sodium BicarbonateHCID 10943925HCID 10943925, compoundHCID 21993865HCID 21993865, compound

Product 1

HCID 21993889HCID 21993889, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 0.401 g (1.011 mM) of N-[2-(3-phenylpropan-1-yl)-2,3-dihydro-1H-isoindol-5-ylmethyl]-phthalimide in 20 ml of ethanol was added 0.05 ml (1.11 mM) of hydrazine monohydrate and the mixture was refluxed for 2 hours. After cooling to room temperature, the precipitate that had formed was filtered off and washed with ethanol. From the pooled filtrate, the solvent was distilled off. The resulting crude N-[2-(3-phenylpropan-1-yl)-2,3-dihydro-1H-isoindol-5-yl]methylamine was not purified but used as it was in the next reaction. To a solution of 0.22 g (1.21 mM) of 5-thia-1,8b-diazaacenaphthylene-4-carboxylic acid, the above crude N-t2-(3-phenylpropan-1-yl)-2,3-dihydro-1H-isoindol-5-yl]methylamine, and 0.17 ml (1.21 mM) of triethylamine in 20 ml of N,N-dimethylformamide was added 0.18 ml (1.21 mM) of diethyl cyanophosphate dropwise at room temperature with constant stirring and the mixture was stirred at the prevailing temperature for 3 days. This reaction mixture was poured in aqueous solution of sodium hydrogen carbonate and extracted with 3 portions of ethyl acetate. The organic layers were pooled and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate to ethyl acetate-methanol=9/1) to provide the title compound.

Workup

  1. temperaturethe mixture was refluxed for 2 hours
  2. customthe precipitate that had formed
  3. filtrationwas filtered off
  4. washwashed with ethanol
  5. distillationFrom the pooled filtrate, the solvent was distilled off
  6. customThe resulting crude N-[2-(3-phenylpropan-1-yl)-2,3-dihydro-1H-isoindol-5-yl]methylamine was not purified
  7. customwas in the next reaction
  8. stirringthe mixture was stirred at the prevailing temperature for 3 days
  9. extractionextracted with 3 portions of ethyl acetate
  10. dry with materialdried over MgSO4
  11. distillationthe solvent was distilled off under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (ethyl acetate to ethyl acetate-methanol=9/1)

Sources & evidence

ORD record
ord-d6a65814b46749fab88f50110d24fad0
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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