4-Methylmorpholine → HCID 178472449, compound

HRID 1087971Notes

Reaction equation

HRID 1087971 reaction equation
CN1CCOCC1.N#N.[C:10]([NH:13][C@H:14]([C:30]([OH:32])=O)[CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])(=[O:12])[CH3:11].C(N=C=NCCCN(C)C)C.[C:44]([O:48][C:49](=[O:73])[CH:50]([CH2:71][NH2:72])[CH2:51][C:52]1([C:57](=[O:70])[NH:58][C@H:59]2[CH2:64][CH2:63][C@@H:62]([C:65]([O:67][CH2:68][CH3:69])=[O:66])[CH2:61][CH2:60]2)[CH2:56][CH2:55][CH2:54][CH2:53]1)([CH3:47])([CH3:46])[CH3:45]>ClCCl>[C:44]([O:48][C:49](=[O:73])[CH:50]([CH:71]([C:30](=[O:32])[C@H:14]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])[NH:13][C:10](=[O:12])[CH3:11])[NH2:72])[CH2:51][C:52]1([C:57](=[O:70])[NH:58][C@H:59]2[CH2:60][CH2:61][C@@H:62]([C:65]([O:67][CH2:68][CH3:69])=[O:66])[CH2:63][CH2:64]2)[CH2:56][CH2:55][CH2:54][CH2:53]1)([CH3:46])([CH3:45])[CH3:47]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 86744253N2 acetyl-N6-benzyloxycarbonyl-L-lysineHCID 178472446HCID 178472446, compound

Product 1

HCID 178472449HCID 178472449, compoundYield 70,920.398%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

1-Hydrobenztriazole (207 mg, 1.53 mmole) and N-methylmorpholine (235 mg, 2.36 mmole) were added to a stirred solution of N2 -acetyl-N6 -benzyloxycarbonyl-L-lysine (456 mg, 1.41 mmole) in dry dichloromethane at 0° C., followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (361 mg). The solution was stirred at 0° C. for 20 minutes and 3-{1-[(cis-4-ethoxycarbonylcyclohexyl)-carbamoyl]cyclopentyl}-2-(aminomethyl)propanoic acid t-butyl ester (500 mg, 1.18 mmole) in dichloromethane (10 ml) was added in one portion and the reaction mixture allowed to warm to room temperature and stirred for 16 hours. The solution was concentrated under vacuum to a volume of 10 ml and partitioned between ethyl acetate and water. The organic phase was washed with water (2×50 ml), 2M hydrochloric acid (50 ml, 2×25 ml), sodium bicarbonate solution (2×25 ml) and brine and then dried (MgSO4) and the solvent evaporated. The residue was chromatographed on silica eluting with ethyl acetate to give the title compound (610 g, 71%). Found: C, 63.34; H, 8.61; N, 7.45. C39H60N4O9 (0.25 H2O) requires C, 63.48; H, 8.33; N, 7.59%.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 16 hours
  3. concentrationThe solution was concentrated under vacuum to a volume of 10 ml
  4. custompartitioned between ethyl acetate and water
  5. washThe organic phase was washed with water (2×50 ml), 2M hydrochloric acid (50 ml, 2×25 ml), sodium bicarbonate solution (2×25 ml) and brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent evaporated
  8. customThe residue was chromatographed on silica eluting with ethyl acetate

Sources & evidence

ORD record
ord-706b27b86ff74c389c95e229aa0d8625
Source dataset
uspto-grants-1990_10
Patent number
US04960792

Reaction notes

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