1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 503192, compound

HRID 977301Notes

Reaction equation

HRID 977301 reaction equation
[C:1]([NH:5][C:6]([C@@H:8]1[CH2:13][C@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:11][CH2:10][N:9]1[CH2:20][C@@H:21]([OH:41])[C@@H:22]([NH:30]C(OCC1C=CC=CC=1)=O)[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li].[N:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[CH2:49][O:50][C:51]([NH:53][C@H:54]([C:59]([OH:61])=O)[C@H:55]([CH2:57][CH3:58])[CH3:56])=[O:52].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C>CN(C=O)C.CCOCC.[Pd].CO>[C:1]([NH:5][C:6]([C@@H:8]1[CH2:13][C@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:11][CH2:10][N:9]1[CH2:20][C@@H:21]([OH:41])[C@@H:22]([NH2:30])[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3].[C:1]([NH:5][C:6]([C@@H:8]1[CH2:13][C@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:11][CH2:10][N:9]1[CH2:20][C@@H:21]([OH:41])[C@@H:22]([NH:30][C:59](=[O:61])[C@H:54]([C@H:55]([CH2:57][CH3:58])[CH3:56])[NH:53][C:51]([O:50][CH2:49][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][N:43]=1)=[O:52])[CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

11

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 503167HCID 503167, compoundHCID 3028194LithiumHCID 54304856HCID 54304856, compound

Product 2

HCID 503192HCID 503192, compoundYield 161.8%HCID 22870891HCID 22870891, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

N-tert-butyl-1-{3(S)-amino-2(R)-hydroxy-4-phenylbutyl}-4(R)-phenylpiperidine-2(S)-carboxamide {prepared by hydrogenolysis (5% Pd/C, 1 atmosphere, MeOH, 2 h) from 0.605 mg (0.108 mmol) of N-tert-butyl-1-{3(S)-(benzyloxycarbonylamino)-2(R)-hydroxy-4-phenylbutyl}-4(R)-phenylpiperidine-2(S)-carboxamide (see entry 1 of Table I)} was dissolved in DMF (1.6 mL). The lithium salt of N-{(2-pyridinylmethoxy)carbonyl}isoleucine (586 mg, 0.228 mmol), 1-hydroxybenzotriazole (32 mg, 0.237 mmol) and N-ethyl-N'-{3-(dimethylamino)propyl}carbodiimide (45.4 mg, 0,237 mmol) were added to the solution. The mixture was stirred at room temperature for 18 h. Thereafter, the reaction mixture was diluted with Et2O, washed with H2O, a saturated aqueous solution of NaHCO3 (2×) and brine, dried (MgSO4) and evaporated to dryness. The resulting yellow oil was purified by flash chromatography (SiO2, eluent: CHCl3, MeOH, 97.5:2.5 and then 95:5) to give the title compound as a white solid (58.7 mg). FAB mass spectrum, m/z: 672 (M+H)+.

Workup

  1. washwashed with H2O
  2. dry with materiala saturated aqueous solution of NaHCO3 (2×) and brine, dried (MgSO4)
  3. customevaporated to dryness
  4. customThe resulting yellow oil was purified by flash chromatography (SiO2, eluent

Sources & evidence

ORD record
ord-2b0d3b9e2c03479d8b26c9a25ab2512b
Source dataset
uspto-grants-1997_03
Patent number
US05614533

Reaction notes

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