HCID 86602700, compound → HCID 57025749, compound

HRID 1375011Notes

Reaction equation

HRID 1375011 reaction equation
[F:1][C:2]([F:55])([F:54])[C:3]1[CH:4]=[C:5]([CH:47]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:49]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][O:23][CH3:24])[CH2:17]2)[CH2:10][C@H:9]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([N:33]=C(C2C=CC=CC=2)C2C=CC=CC=2)[CH:27]=1)=[O:7].[H][H]>CO.[Pd]>[F:53][C:50]([F:51])([F:52])[C:48]1[CH:47]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:54])[F:55])[CH:49]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][O:19][C@H:18]([CH2:22][O:23][CH3:24])[CH2:17]2)[CH2:10][C@H:9]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[C:28]([NH2:33])[CH:27]=1)=[O:7]

Participants

5

Reactant 2

HCID 86602700HCID 86602700, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 57025749HCID 57025749, compoundYield 35.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-(diphenylmethyleneamino)-4-methylbenzyl]-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]piperazine (65 mg) in methanol was subjected to hydrogenolysis (3 atm hydrogen pressure) using 10% palladium on carbon (6 mg, 50% wet) at 50° C. for 16 hours. After cooling, the mixture was filtered and the filtrate was evaporated in vacuo. Ethyl acetate and water were added to the residue and the organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by column chromatography on silica gel (NH-DM1020, Fuji Silysis Chemical Ltd.) with a mixture of hexane and ethyl acetate (1:1) as eluent to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3-amino-4-methylbenzyl)-4-[2-[(2S)-2-(methoxymethyl)morpholino]ethyl]-piperazine (18 mg). To a solution of the obtained compound in methanol was added 4N hydrogen chloride in ethyl acetate (0.05 ml) and the mixture was evaporated in vacuo to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3-amino-4-methylbenzyl)-4-[2-((2S)-2-(methoxymethyl)morpholino]ethyl]-piperazine trihydrochloride (20 mg).

Workup

  1. customat 50° C.
  2. customfor 16 hours
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered
  5. customthe filtrate was evaporated in vacuo
  6. additionEthyl acetate and water were added to the residue
  7. customthe organic layer was separated
  8. dry with materialdried over magnesium sulfate
  9. customevaporated in vacuo
  10. customThe residue was purified by column chromatography on silica gel (NH-DM1020, Fuji Silysis Chemical Ltd.) with a mixture of hexane and ethyl acetate (1:1) as eluent

Sources & evidence

ORD record
ord-f2cb66e44c9643e0b7b97f514dd6b3d1
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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