4-Methylmorpholine → 4-{[4-N-(Benzhydryloxycarbonyl)-cytosin-1-yl]-acetyl}-1-(2-nitro-benzenesulfonyl)-piperazin-2-one

HRID 1794947Notes

Reaction equation

HRID 1794947 reaction equation
[CH:1]([O:14][C:15]([NH:17][C:18]1[CH:23]=[CH:22][N:21]([CH2:24][C:25]([N:27]([CH2:32][CH2:33][NH:34][S:35]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=2[N+:44]([O-:46])=[O:45])(=[O:37])=[O:36])[CH2:28][C:29]([OH:31])=O)=[O:26])[C:20](=[O:47])[N:19]=1)=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O>C1COCC1>[CH:1]([O:14][C:15]([NH:17][C:18]1[CH:23]=[CH:22][N:21]([CH2:24][C:25]([N:27]2[CH2:32][CH2:33][N:34]([S:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[N+:44]([O-:46])=[O:45])(=[O:36])=[O:37])[C:29](=[O:31])[CH2:28]2)=[O:26])[C:20](=[O:47])[N:19]=1)=[O:16])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 22222393N-{[4-N-(benzhydryloxycarbonyl)-cytosin-1-yl]-acetyl}-N-[2-(2-nitro-benzenesulfonylamino)-ethyl]-glycine

Product 1

HCID 222224354-{[4-N-(Benzhydryloxycarbonyl)-cytosin-1-yl]-acetyl}-1-(2-nitro-benzenesulfonyl)-piperazin-2-oneYield 77.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of N-{[4-N-(benzhydryloxycarbonyl)-cytosin-1-yl]-acetyl}-N-[2-(2-nitro-benzenesulfonylamino)-ethyl]-glycine (1.20 g, 1.8 mmol) in THF (24 mL) was added N-methylmorpholine (0.6 mL, 5.42 mmol) and then the mixture was cooled to −20° C. After stirring for 5 min at the same temperature, isobutyl chloroformate (0.30 mL, 2.31 mmol) was added to the reaction mixture. The resulting mixture was slowly warmed to 0° C. for 1 h. Then the reaction mixture was evaporated in vacuo and dissolved in a mixture of ethyl acetate and acetonitrile. The solution was washed with saturated NaCl solution and dried over sodium sulfate and filtered. The filtrate was evaporated in vacuo and triturated with methanol to precipitate solid. The solid was filtered off, washed with methanol, and dried in vacuo to give the titled compound 0.9 g (77%). 1H-NMR (500 MHz; DMSO-d6) δ 8.35 (t, 1H), 8.12˜7.95 (m, 3H), 7.90 (d, 0.6H), 7.84 (d, 0.4H), 7.48˜7.28 (m, 10H), 6.95 (d, 0.6H), 6.94 (d, 0.4H), 6.79 (s, 1H), 4.82 (s, 1.2H), 4.73 (s, 0.8H), 4.45 (s, 0.8H), 4.27 (s, 1.2H), 4.10˜3.95 (m, 2.4H), 3.95˜3.80 (m, 1.6H).

Workup

  1. additionwas added to the reaction mixture
  2. temperatureThe resulting mixture was slowly warmed to 0° C. for 1 h
  3. customThen the reaction mixture was evaporated in vacuo
  4. dissolutiondissolved in a mixture of ethyl acetate and acetonitrile
  5. washThe solution was washed with saturated NaCl solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customThe filtrate was evaporated in vacuo
  9. customtriturated with methanol
  10. customto precipitate solid
  11. filtrationThe solid was filtered off
  12. washwashed with methanol
  13. customdried in vacuo

Sources & evidence

ORD record
ord-000033b68c534b9396ab3e3313942414
Source dataset
uspto-grants-2006_04
Patent number
US07022851B2

Reaction notes

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