4-Methylmorpholine → dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-[[2-(2-quinolinyl)ethyl]amino]ethyl]carbamate

HRID 54859Notes

Reaction equation

HRID 54859 reaction equation
[CH:1]12C[CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[O:11][C:12]([NH:14][C:15]([CH3:29])([C:26](O)=[O:27])[CH2:16][C:17]1[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=1)=[O:13])[CH2:8]2.[CH3:30]N1CCOCC1.ClC(OCC(C)C)=O.[NH2:45][CH2:46][CH2:47][C:48]1[CH:57]=[CH:56][C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[N:49]=1>C1COCC1>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([CH2:16][C:15]([NH:14][C:12](=[O:13])[O:11][CH:2]([CH2:1][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH3:9])[CH3:30])([CH3:29])[C:26]([NH:45][CH2:46][CH2:47][C:48]2[CH:57]=[CH:56][C:55]3[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=3)[N:49]=2)=[O:27])=[CH:18]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 101763222-(Quinolin-2-yl)ethan-1-amineHCID 148025032-adamantyloxycarbonyl-alpha-methyl-DL-tryptophan

Product 1

HCID 86750758dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-[[2-(2-quinolinyl)ethyl]amino]ethyl]carbamateYield 17.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-22 °C

Procedure

To a stirred solution of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan (1.59 g, 4.0 mmole) in dry THF (50 mL) at -22° C. was added N-methylmorpholine (0.644 g, 6.3 mmole) and isobutyl chloroformate (0.632 g, 4.6 mmole). The mixture was stirred at -22° C. for 1 hour and then a solution of 2-(2-aminoethyl)quinoline (0.690 g, 4.0 mmole) in dry THF (15 mL) was added. After stirring at this temperature 4 hours the reaction mixture was allowed to stir at room temperature 15 hours. The solvent was removed in vacuo and the residue was taken up in EtOAc and washed with 5% citric acid (2×50 mL), water (2×50 mL), 5% NaHCO3 (3×50 mL), water (2×50 mL), and brine (2×50 mL). The organic phase was dried over MgSO4 and the solvent evaporated. The residue was flash chromatographed on silica gel, eluting with EtOAc-n-hexane. The oil obtained was triturated with cold Et2O, yielding the product as an amorphous white solid, (0.38 g, 17%); 1H NMR (CDCl3) δ1.41-1.88 (17H, m), 3.00-3.04 (2H, m), 3.40 (2H, q, J 9.59 Hz), 3.68-3.70 (2H, m), 4.70 (1H, s), 5.43 (1H, br s), 6.90 (1H, d, J 2.23), 6.96-7.22 (4H, m), 7.45-7.55 (2H, m), 7.63-7.70 (2H, m), 7.78 (1H, d, J 8.06), 7.89 (2H, d, J 8.10), 8.03 (1H, d, J 8.46).

Workup

  1. stirringAfter stirring at this temperature 4 hours the reaction mixture
  2. stirringto stir at room temperature 15 hours
  3. customThe solvent was removed in vacuo
  4. washwashed with 5% citric acid (2×50 mL), water (2×50 mL), 5% NaHCO3 (3×50 mL), water (2×50 mL), and brine (2×50 mL)
  5. dry with materialThe organic phase was dried over MgSO4
  6. customthe solvent evaporated
  7. customchromatographed on silica gel
  8. washeluting with EtOAc-n-hexane
  9. customThe oil obtained
  10. customwas triturated with cold Et2O

Sources & evidence

ORD record
ord-7a2ee00027d0496bad6ffeedbd46d88f
Source dataset
uspto-grants-1997_04
Patent number
US05622983

Reaction notes

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