Methanesulfonyl chloride → Boc-saxagliptin

HRID 1808687Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1808687
[CH3:1][C:2]([CH3:23])([O:4][C:5]([NH:7][C@@H:8]([C:12]12[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][C:14]([OH:22])([CH2:15]3)[CH2:13]1)[CH2:19]2)[C:9](O)=[O:10])=[O:6])[CH3:3].CS(Cl)(=O)=O.C(N(C(C)C)CC)(C)C.Cl.[C@H:39]12[CH2:44][C@H:43]1[CH2:42][C@@H:41]([C:45]([NH2:47])=O)[NH:40]2.OC1C2N=NNC=2C=CC=1>C1COCC1>[C:45]([C@@H:41]1[CH2:42][C@H:43]2[C@H:39]([CH2:44]2)[N:40]1[C:9](=[O:10])[C@H:8]([C:12]12[CH2:19][CH:18]3[CH2:17][CH:16]([CH2:15][C:14]([OH:22])([CH2:20]3)[CH2:13]1)[CH2:21]2)[NH:7][C:5]([O:4][C:2]([CH3:23])([CH3:1])[CH3:3])=[O:6])#[N:47]

Komponenten

7

Edukt 5

HCID 31297Methanesulfonyl chlorideHCID 81531Diisopropylethylamine2×HCID 11564521(1S,3S,5S)-2-Azabicyclo[3.1.0]hexane-3-carboxamide hydrochlorideHCID 11723843(2S)-((tert-Butoxycarbonyl)amino)(3-hydroxytricyclo(3.3.1.1 3,7)dec-1-yl)acetic acid2×HCID 178418300HCID 178418300, Verbindung

Produkt 1

HCID 51358360Boc-saxagliptin

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-6 °C

Versuchsvorschrift

A 2 L three-necked flask equipped with a thermometer, a mechanical stirrer and a gas inlet was charged with (αS)-α[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid (Formula 3) (50 grams, 153.8 mmol). THF (200 ml) was added and stirred to produce a clear solution. The solution was cooled to −6° C. in an acetone-dry ice-water bath. Methanesulfonyl chloride (Mes-C1) (13.1 ml, 169 mmol, 1.1 equivalents) was then added as a single portion followed by diisopropylethylamine (94 ml, 539 mmol, 1.1 equivalents). The diisopropylethylamine was added slowly over a period of about 4 minutes to keep the internal temperature below 8° C. The reaction mixture was stirred at 0° C. until all acid was converted to mixed anhydride. (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide hydrochloride salt (32.5 grams, 200 mmol, 1.1 equivalents) and hydroxybenzotriazole (HOBT) (1.04 grams, 7.6 mmol, 0.05 equivalents) were then added in a single portion and the flask was removed from the cooling bath. The reaction mixture was stirred at room temperature for 2 hours and then left overnight at room temperature.

Aufarbeitung

  1. customA 2 L three-necked flask equipped with a thermometer, a mechanical stirrer and a gas inlet
  2. customto produce a clear solution
  3. customthe internal temperature below 8° C
  4. stirringThe reaction mixture was stirred at 0° C. until all acid
  5. customthe flask was removed from the cooling bath
  6. stirringThe reaction mixture was stirred at room temperature for 2 hours

Quellen und Nachweise

ORD-Eintrag
ord-e2e69f14f60b4198b51fcc5445c093ce
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08361761B2

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