methyl (R)-{2-[N-{1-[(2,6-dimethoxy-4-methylphenyl)pentylcarbamoyl]-5-(benzyloxycarbonylamino)pentyl}carbamoyl]indol-1-yl}acetate → methyl (R)-{2-[N-{1-[(2,6-dimethoxy-4-methylphenyl)pentylcarbamoyl]-5-aminopentyl}carbamoyl]indol-1-yl}acetate

HRID 2927Notes

Reaction equation

HRID 2927 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([O:10][CH3:11])[C:4]=1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([C@H:20]([NH:36][C:37]([C:39]1[N:40]([CH2:48][C:49]([O:51][CH3:52])=[O:50])[C:41]2[C:46]([CH:47]=1)=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])[CH2:21][CH2:22][CH2:23][CH2:24][NH:25]C(OCC1C=CC=CC=1)=O)=[O:19]>CO.[Pd]>[CH3:11][O:10][C:5]1[CH:6]=[C:7]([CH3:9])[CH:8]=[C:3]([O:2][CH3:1])[C:4]=1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][NH:17][C:18]([C@H:20]([NH:36][C:37]([C:39]1[N:40]([CH2:48][C:49]([O:51][CH3:52])=[O:50])[C:41]2[C:46]([CH:47]=1)=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])[CH2:21][CH2:22][CH2:23][CH2:24][NH2:25])=[O:19]

Participants

4

Reactant 1

HCID 86752318methyl (R)-{2-[N-{1-[(2,6-dimethoxy-4-methylphenyl)pentylcarbamoyl]-5-(benzyloxycarbonylamino)pentyl}carbamoyl]indol-1-yl}acetate

Product 1

HCID 86752317methyl (R)-{2-[N-{1-[(2,6-dimethoxy-4-methylphenyl)pentylcarbamoyl]-5-aminopentyl}carbamoyl]indol-1-yl}acetateYield 85%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

5.6 g of methyl (R)-{2-[N-{1-[(2,6-dimethoxy-4-methylphenyl)pentylcarbamoyl]-5-(benzyloxycarbonylamino)pentyl}carbamoyl]indol-1-yl}acetate (EXAMPLE 66) are dissolved in 170 ml of methanol and 0.56 g of 10% Pd/C is added thereto. Hydrogenation is carried out under a pressure of 3 bar and the reaction mixture is left at 30° C., while maintaining this pressure, for 18 hours. After cooling, the catalyst is filtered over a bed of celite and evaporation is carried out to dryness. The residual oil is purified by flash chromatography on silica gel, eluent: CH2Cl2 /CH3 OH/AcOH 90/10/0.5 (v/v/v) in order to obtain white crystals of methyl (R)-{2-[N-{1-[(2,6-dimethoxy-4-methylphenyl)pentylcarbamoyl]-5-aminopentyl}carbamoyl]indol-1-yl}acetate, M.p.=78° C., [α]D20 =-47.6° (c=1, CH3OH), Yield: 85%.

Workup

  1. waitthe reaction mixture is left at 30° C.
  2. temperaturewhile maintaining this pressure
  3. temperatureAfter cooling
  4. filtrationthe catalyst is filtered over a bed of celite and evaporation
  5. customThe residual oil is purified by flash chromatography on silica gel, eluent

Sources & evidence

ORD record
ord-29290da4f651485f9a89caa1ac100820
Source dataset
uspto-grants-1998_03
Patent number
US05731340

Reaction notes

Loading…