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Ethyl Acetate → 2-chloro-N-[2-chloro-5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethoxy)benzamide

HRID 1800633
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1800633
[NH2:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][C:23]=1[Cl:24])[O:5][C:6]1[N:11]=[C:10]2[S:12][C:13]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])=[N:14][C:9]2=[CH:8][CH:7]=1.[Cl:25][C:26]1[C:34]([O:35][C:36]([C:39]#[N:40])([CH3:38])[CH3:37])=[CH:33][CH:32]=[CH:31][C:27]=1[C:28](O)=[O:29].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(OCC)(=O)C>N1C=CC=CC=1.O>[Cl:25][C:26]1[C:34]([O:35][C:36]([C:39]#[N:40])([CH3:37])[CH3:38])=[CH:33][CH:32]=[CH:31][C:27]=1[C:28]([NH:1][C:2]1[CH:3]=[C:4]([O:5][C:6]2[N:11]=[C:10]3[S:12][C:13]([NH:15][C:16]([CH:18]4[CH2:20][CH2:19]4)=[O:17])=[N:14][C:9]3=[CH:8][CH:7]=2)[CH:21]=[CH:22][C:23]=1[Cl:24])=[O:29]
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Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57384284N-[5-(3-amino-4-chlorophenoxy) [1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamideHCID 684177462-Chloro-3-(1-cyano-1-methylethoxy)benzoic acid

Produkt 1

HCID 59507025
2-chloro-N-[2-chloro-5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethoxy)benzamide
Ausbeute 24,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

N-[5-(3-Amino-4-chlorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (200 mg, 0.554 mmol) produced in Example C118(ii), 2-chloro-3-(1-cyano-1-methylethoxy)benzoic acid (199 mg, 0.830 mmol) produced in Example C70(i) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (422 mg, 1.11 mmol) were suspended in pyridine (2 mL), and the suspension was stirred at 60° C. for 16 hr. After cooling to room temperature, ethyl acetate (100 mL) and water (80 mL) were added, and the mixture was partitioned. The organic layer was washed with saturated brine (50 mL), dried over anhydrous magnesium sulfate, and dried under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0) and basic silica gel column chromatography (ethyl acetate/methanol=100/0→90/10), and triturated with diisopropyl ether to give the title compound (78 mg, 24%) as white crystals.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned
  3. washThe organic layer was washed with saturated brine (50 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customdried under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60→100/0) and basic silica gel column chromatography (ethyl acetate/methanol=100/0→90/10)
  7. customtriturated with diisopropyl ether

Quellen und Nachweise

ORD-Eintrag
ord-cb5d80c9166647f09256df448af876d2
Quelldatensatz
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08344135B2

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