4-Methylmorpholine → N-({4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy)-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-cyclohexyl-D-alanine

HRID 1176073Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1176073
[Si:1]([O:8][C@H:9]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:19][CH:18]=2)[C@@H:13]1[C:31]1[CH:41]=[CH:40][C:34]([O:35][CH2:36][C:37](O)=[O:38])=[CH:33][CH:32]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:78][CH2:79][C:80]([NH:82][C@@H:83]([C:91]([OH:93])=[O:92])[CH2:84][CH:85]1[CH2:90][CH2:89][CH2:88][CH2:87][CH2:86]1)=[O:81]>CN(C=O)C>[Si:1]([O:8][C@H:9]([C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[CH:21][CH:22]=2)[C@@H:13]1[C:31]1[CH:32]=[CH:33][C:34]([O:35][CH2:36][C:37]([NH:78][CH2:79][C:80]([NH:82][C@@H:83]([C:91]([OH:93])=[O:92])[CH2:84][CH:85]2[CH2:90][CH2:89][CH2:88][CH2:87][CH2:86]2)=[O:81])=[O:38])=[CH:40][CH:41]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842930Glycyl-3-cyclohexyl-D-alanineHCID 68774413{4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

Produkt 1

HCID 86628616N-({4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy)-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetyl)glycyl-3-cyclohexyl-D-alanine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

{4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid (Method 8) (25.1 mg, 0.040 mmol) was dissolved in DMF (1 ml, dry). N-methylmorpholine (13 μl, 121 mmol) was added and the reaction mixture was stirred at 30° C. for five minutes. TBTU (20.1 mg, 0.063 mmol) was added and the reaction mixture was stirred at 30° C. for 1 hour. Glycyl-3-cyclohexyl-D-alanine (12.5 mg, 0.055 mmol) was added and the reaction mixture was stirred for 2 hours. The reaction mixture was purified with preparative HPLC on a C8 column. A gradient from 10 to 100% MeCN in 0.1M NH4OAc buffer was used as eluent. Most of the MeCN was removed under reduced pressure. The residue was diluted with water and lyophilised to give the title compound, M/z: 921 (M−1).

Aufarbeitung

  1. stirringthe reaction mixture was stirred at 30° C. for 1 hour
  2. stirringthe reaction mixture was stirred for 2 hours
  3. customThe reaction mixture was purified with preparative HPLC on a C8 column
  4. customMost of the MeCN was removed under reduced pressure
  5. additionThe residue was diluted with water

Quellen und Nachweise

ORD-Eintrag
ord-685892e3f8d746fcbc9fcaa5d7dc0f9a
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07842684B2

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