Methylamine → HCID 10281683, compound

HRID 2307712Notes

Reaction equation

HRID 2307712 reaction equation
[CH:1]1[C:6]2[C:7]([O:9][C:10](=[O:11])[C:5]=2[CH:4]=[C:3]2[C:12]([O:14][C:15](=[O:16])[C:2]=12)=[O:13])=[O:8].[CH:17]([N:20](C(C)C)CC)(C)C.[O:26]([C:33]1[CH:34]=[C:35]([CH:48]=[CH:49][CH:50]=1)[CH2:36][NH:37][C@@H:38]1[C:47]2[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH2:41][CH2:40][CH2:39]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CN>C1COCC1>[CH3:17][NH:20][C:7]([C:6]1[CH:1]=[C:2]([C:15]([N:37]([CH2:36][C:35]2[CH:48]=[CH:49][CH:50]=[C:33]([O:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:34]=2)[C@@H:38]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[CH2:41][CH2:40][CH2:39]2)=[O:16])[C:3]([C:12]([OH:14])=[O:13])=[CH:4][C:5]=1[C:10]([OH:9])=[O:11])=[O:8]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 6966Pyromellitic dianhydrideHCID 81531DiisopropylethylamineHCID 69721319HCID 69721319, compound

Product 1

HCID 10281683HCID 10281683, compoundYield 12.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,2,4,5-Benzenetetracarboxylic dianhydride (1.1 g, 5 mmol) in THF (25 mL) was treated with diisopropylethyl amine (1.6 mL, 9.2 mmol) dropwise at −78° C. and then treated with N-(3-phenoxybenzyl)-N-[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amine (9 mL, 4.5 mmol, 0.5M solution in ClCH2CH2Cl) dropwise. After allowing the reaction mixture to gradually warm to room temperature overnight, the mixture was recooled to −78° C. and treated with methylamine (2.5 mL, 5 mmol, 2M in MeOH) dropwise. The reaction mixture was again allowed to slowly warm to room temperature. The organics were removed under reduced pressure and the residue was dissolved in ethyl acetate (25 mL). The ethyl acetate solution was washed with 1N HCl (2×5 mL), brine (5 mL), dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatographed (silica gel, 5:95 MeOH:CH2Cl2 to 1:9 MeOH:CH2Cl2) to provide a solid. The solid was further purified by RP-HPLC to provide the title compound as an off-white solid (319 mg, 12%).

Workup

  1. customwas recooled to −78° C.
  2. temperatureto slowly warm to room temperature
  3. customThe organics were removed under reduced pressure
  4. dissolutionthe residue was dissolved in ethyl acetate (25 mL)
  5. washThe ethyl acetate solution was washed with 1N HCl (2×5 mL), brine (5 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate concentrated under reduced pressure
  9. customThe residue was purified by flash
  10. customchromatographed (silica gel, 5:95 MeOH:CH2Cl2 to 1:9 MeOH:CH2Cl2)
  11. customto provide a solid
  12. customThe solid was further purified by RP-HPLC

Sources & evidence

ORD record
ord-6adafe80f51e4c3495ca5b16fa4c8197
Source dataset
uspto-grants-2004_12
Patent number
US06831193B2

Reaction notes

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