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4-Methylmorpholine → N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-b,b-dimethyl-D-phenylalanine

HRID 603902
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 603902
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([OH:40])[CH2:11][S:12][C@H:13]3[C:16](=[O:17])[N:15]([C:18]4[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=4)[C@@H:14]3[C:25]3[CH:39]=[CH:38][C:28]([O:29]CC(NCC(O)=O)=O)=[CH:27][CH:26]=3)=[CH:9][C:4]=2[O:3][CH2:2]1.C[N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.CN(C([O:55]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O.[CH3:77][C:78]([CH3:90])([C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1)[C@H:79]([C:81]([OH:83])=[O:82])[NH2:80]>CN(C=O)C>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([OH:40])[CH2:11][S:12][C@H:13]3[C:16](=[O:17])[N:15]([C:18]4[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=4)[C@@H:14]3[C:25]3[CH:39]=[CH:38][C:28]([O:29][CH2:44][C:43]([NH:42][CH2:47][C:46]([NH:80][C@@H:79]([C:81]([OH:83])=[O:82])[C:78]([CH3:90])([CH3:77])[C:84]4[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=4)=[O:45])=[O:55])=[CH:27][CH:26]=3)=[CH:9][C:4]=2[O:3][CH2:2]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842897beta,beta-dimethyl-D-phenylalanine trifluoroacetateHCID 67271334N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycine

Produkt 1

HCID 67271104
N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-b,b-dimethyl-D-phenylalanine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

To a stirred solution of N-({4-[(2R,3R)-3-{[2-(1,3-benzodioxol-5-yl)-2-hydroxyethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycine (15.6 mg, 0.027 mmol) in DMF (2 ml) was added N-methylmorpholine (15 μl, 0.091 mmol). TBTU (12.2 mg, 0.038 mmol) was added and the reaction mixture was stirred at 30° C. for 1 hour. β,β-dimethyl-D-phenylalanine trifluoroacetate (10.2 mg, 0.033 mmol) was added and the mixture was stirred at ambient temperature overnight. The solution was purified with preparative HPLC on a C8 column, UV 240/260 nm. A gradient from 20 to 45% 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 organic phase was passed through a phase separator and concentrated under reduced pressure. The residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained. H-NMR (400 MHz, DMSO-d6): 1.28 (d, 6H), 2.74-2.92 (m, 2H), 3.58-3.82 (m, 2H) 4.30-4.21 (m, 1H), 4.46 (s, 2H), 4.53-4.65 (m, 2H) 5.00 (b, 0.5H), 5.03 (b, 0.5H), 5.53 (b, 1H), 5.90-5.94 (m, 2H), 6.70-6.79 (m, 2H), 6.82 (s, 1H), 6.90-6.98 (m, 2H), 7.07-7.15 (m, 3H), 7.18-7.26 (m, 4H), 7.27-7.37 (m, 4H), 7.78 (b, 1H), 8.19 (t, 1H). M/z: 742.68 (M−1).

Aufarbeitung

  1. stirringthe mixture was stirred at ambient temperature overnight
  2. customThe solution was purified with preparative HPLC on a C8 column, UV 240/260 nm
  3. customThe pure fractions were collected
  4. customthe MeCN was removed under reduced pressure
  5. extractionextracted with DCM
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in MeCN

Quellen und Nachweise

ORD-Eintrag
ord-d401a8d447334797a4864bfa19e9ed8e
Quelldatensatz
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07906502B2

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