4-Methylmorpholine → HCID 66843220, Verbindung

HRID 254063Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 254063
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([OH:36])=O)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:68][C:69]1[CH:82]=[CH:81][C:72]([CH2:73][S:74][CH2:75][C@H:76]([C:78]([OH:80])=[O:79])[NH2:77])=[CH:71][CH:70]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][CH:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[OH:16])[C@H:9]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([NH:77][C@@H:76]([C:78]([OH:80])=[O:79])[CH2:75][S:74][CH2:73][C:72]3[CH:81]=[CH:82][C:69]([CH3:68])=[CH:70][CH:71]=3)=[O:36])=[O:31])=[CH:37][CH:38]=2)=[CH:4][CH:3]=1

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7314856S-4-Methylbenzyl-D-cysteineHCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Produkt 1

HCID 66843220HCID 66843220, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

To a stirred solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine, (19.9 mg, 0.037 mmol) in DMF (2.0 ml) was added N-methylmorpholine (15 μl, 0.14 mmol). TBTU (14.4 mg, 0.045 mmol) was added and the mixture was stirred at 30° C. for 45 minutes. S-(4-methylbenzyl)-D-cysteine (10.5 mg, 0.047 mmol) was added and the mixture was stirred at 30° C. for 1 hour. The formation of the ketone of the title compound was confirmed. M/z: 748.02 (M+1). Methanol (2 ml) and sodium borohydride (14.7 mg, 0.39 mmol) were added the mixture was stirred for 30 minutes. Ammonium acetate (20 mg) was added and the methanol was removed under reduced pressure. The remaining DMF-solution was purified with preparative HPLC on a C8 column, UV-detection 240/260 nm. A gradient from 20 to 50% MeCN in 0.1M NH4OAc buffer was used as eluent. The pure fractions were collected and the MeCN was removed under reduced pressure. The remaining water solution was acidified to pH 1 with HCl (1M) and extracted with DCM. The combined organic phases were concentrated and the residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained as a white solid (8.7 mg, 31.5%). H-NMR (400 MHz, DMSO-d6): 2.24 (s, 3H), 2.60-2.68 (m, 1H), 2.72-2.79 (m, 1H), 2.86-2.94 (m, 2H), 3.68 (s, 2H), 3.82 (d, 2H), 4.25 (d, 0.5H), 4.27 (d, 0.5H), 4.39-4.46 (m, 1H), 4.52 (s, 2H), 4.67-4.77 (m, 1H), 5.03 (d, 0.5H), 5.06 (d, 0.5H), 5.60-5.67 (bs, 1H), 6.98 (d, 2H), 7.05-7.18 (m, 8H), 7.20-7.25 (m, 2H), 4.30-4.39 (m, 4H), 8.23-8.32 (m, 2H), 12.80-12.95 (bs, 1H). M/z: 748.04 (M−1).

Aufarbeitung

  1. stirringthe mixture was stirred at 30° C. for 1 hour

Quellen und Nachweise

ORD-Eintrag
ord-f2ba7577a36c4d3e8594049a905d1b09
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07871998B2

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