Methyl chloroformate → 2-((3-(1-(1-Acetylazetidin-3-yl)piperidin-4-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921700Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921700
[NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][CH:8]([C:11]3[C:12]([Cl:35])=[C:13]([NH:19][C:20]4[N:25]=[C:24]([NH:26][CH:27]5[CH2:29][CH2:28]5)[C:23]5=[N:30][CH:31]=[C:32]([C:33]#[N:34])[N:22]5[N:21]=4)[CH:14]=[C:15]([C:17]#[N:18])[CH:16]=3)[CH2:7][CH2:6]2)[CH2:2]1.C(N([CH2:41][CH3:42])CC)C.ClC(OC)=[O:45]>C(Cl)Cl>[C:41]([N:1]1[CH2:2][CH:3]([N:5]2[CH2:6][CH2:7][CH:8]([C:11]3[C:12]([Cl:35])=[C:13]([NH:19][C:20]4[N:25]=[C:24]([NH:26][CH:27]5[CH2:28][CH2:29]5)[C:23]5=[N:30][CH:31]=[C:32]([C:33]#[N:34])[N:22]5[N:21]=4)[CH:14]=[C:15]([C:17]#[N:18])[CH:16]=3)[CH2:9][CH2:10]2)[CH2:4]1)(=[O:45])[CH3:42]

Komponenten

5

Edukt 3

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 86708575HCID 86708575, Verbindung

Produkt 1

HCID 867085762-((3-(1-(1-Acetylazetidin-3-yl)piperidin-4-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a suspension of 2-((3-(1-(azetidin-3-yl)piperidin-4-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 318) (25 mg, 0.051 mmol) and triethylamine (0.014 mL, 0.102 mmol) in CH2Cl2 (1.5 mL) was added dropwise acetyl chloride (4.41 mg, 0.056 mmol, diluted with DCM, 10V % in DCM, 44 uL) at 0° C. The suspension converted to a clear solution in a few min, and continued stirring at 0° C. for 1 h. Removal of the solvent, and the crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 20-mM ammonium acetate; Gradient: 20-60% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation left the titled product (15.6 mg)

Aufarbeitung

  1. customRemoval of the solvent
  2. customthe crude material was purified via preparative LC/MS with the following conditions
  3. waitGradient: 20-60% B over 20 minutes
  4. customa 5-minute hold
  5. additionFractions containing the desired product
  6. customdried via centrifugal evaporation
  7. waitleft the titled product (15.6 mg)

Quellen und Nachweise

ORD-Eintrag
ord-1a09ea90c87142e8bbb5f25a94e0ee81
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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