O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate → Methyl 4-(1-(5-chloro-2-(3-((4-fluorophenoxy)methyl)azetidin-1-yl)nicotinamido)cyclopropyl)benzoate

HRID 72507Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 72507
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:14][CH:13]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:12]2)=[C:6]([CH:10]=1)[C:7](O)=[O:8].F[P-](F)(F)(F)(F)F.ClC1C=CC2N=NN(OC(N(C)C)=[N+](C)C)C=2C=1.Cl.[NH2:50][C:51]1([C:54]2[CH:63]=[CH:62][C:57]([C:58]([O:60][CH3:61])=[O:59])=[CH:56][CH:55]=2)[CH2:53][CH2:52]1>[NH4+].[Cl-]>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:12][CH:13]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[CH2:14]2)=[C:6]([CH:10]=1)[C:7]([NH:50][C:51]1([C:54]2[CH:63]=[CH:62][C:57]([C:58]([O:60][CH3:61])=[O:59])=[CH:56][CH:55]=2)[CH2:53][CH2:52]1)=[O:8]

Komponenten

5

Edukt 3

HCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 66824369Methyl 4-(1-aminocyclopropyl)benzoate hydrochlorideHCID 679583595-Chloro-2-(3-((4-fluorophenoxy)methyl)azetidin-1-yl)nicotinic acid

Produkt 1

HCID 67958882Methyl 4-(1-(5-chloro-2-(3-((4-fluorophenoxy)methyl)azetidin-1-yl)nicotinamido)cyclopropyl)benzoateAusbeute 64,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

A mixture of 5-chloro-2-(3-((4-fluorophenoxy)methyl)azetidin-1-yl)nicotinic acid (D113) (55.4 mg, 0.161 mmol), O-(6-Chlorobenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HCTU) (66.8 mg, 0.161 mmol) and N,N-disopropylethylamine (0.072 ml, 0.403 mmol) was stirred 30 min at room temperature. Methyl 4-(1-aminocyclopropyl)benzoate hydrochloride (D7) (37.8 mg, 0.161 mmol) was added and the reaction mixture stirred overnight at room temperature. NH4Cl saturated solution (20 ml) was added and the mixture was extracted with ethylacetate (3×10 ml). The residue obtained after solvent evaporation was purified by SPE-Si cartridge (10 g) eluting dichloromethane. Collected fractions, after solvent evaporation, afforded the title compound (D163) (52.6 mg).

Aufarbeitung

  1. stirringthe reaction mixture stirred overnight at room temperature
  2. extractionthe mixture was extracted with ethylacetate (3×10 ml)
  3. customThe residue obtained
  4. customafter solvent evaporation
  5. customwas purified by SPE-Si cartridge (10 g)
  6. washeluting dichloromethane
  7. customCollected fractions, after solvent evaporation

Quellen und Nachweise

ORD-Eintrag
ord-f08ec3ba944541f6b35c32226025d65e
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828987B2

Notizen zur Reaktion

Wird geladen…