Ammonia → N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(3-methoxyphenyl)propan-2-yl]-5-methyl-1,3,4-oxadiazole-2-carboxamide

HRID 1098959

Reaktionsgleichung

Reaktionsgleichung von HRID 1098959
[CH3:1][C:2]1[O:6][C:5]([C:7]([O-:9])=O)=[N:4][N:3]=1.[K+].C(Cl)(=O)C(Cl)=O.[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[C:32]3[C:27](=[CH:28][C:29]([O:33][C@H:34]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=4)[C@@H:35]([NH2:37])[CH3:36])=[CH:30][CH:31]=3)[CH:26]=[N:25]2)=[CH:20][CH:19]=1.C(N(CC)C(C)C)(C)C.N>C1COCC1.CCOC(C)=O.C(#N)C>[F:17][C:18]1[CH:19]=[CH:20][C:21]([N:24]2[C:32]3[C:27](=[CH:28][C:29]([O:33][C@H:34]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([O:44][CH3:45])[CH:39]=4)[C@@H:35]([NH:37][C:7]([C:5]4[O:6][C:2]([CH3:1])=[N:3][N:4]=4)=[O:9])[CH3:36])=[CH:30][CH:31]=3)[CH:26]=[N:25]2)=[CH:22][CH:23]=1

Komponenten

9

Edukt 5

HCID 222AmmoniaHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 24820502Potassium 5-methyl-1,3,4-oxadiazole-2-carboxylateHCID 59339733(1R,2S)-1-(1-(4-fluorophenyl)indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine

Produkt 1

HCID 44515376N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(3-methoxyphenyl)propan-2-yl]-5-methyl-1,3,4-oxadiazole-2-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6342AcetonitrileLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

Potassium 5-methyl-[1,3,4]oxadiazole-2-carboxylate (31.8 mg, 0.19 mmol) was mixed with acetonitrile (195 μl). A slurry was formed. The mixture was cooled to 0-5° C. oxalyl chloride (14.99 μl, 0.17 mmol) was added and the reaction was stirred for 1 h at 0-5° C. (1R,2S)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)-1-(3-methoxyphenyl)propan-2-amine (6a, 25 mg, 0.06 mmol) was dissolved in dry THF (400 μl). N,N-diisopropylethylamine (65.6 μl, 0.38 mmol) was added. The THF solution was cooled to 0-5° C. The acid chloride slurry was drop wise added to the amine solution. The reaction was stirred at 0-5° C. After 1.5 h the reaction was poured into a mixture of EtOAc and diluted ammonia (ca 5%). The mixture was shaken, the organic layer collected. The water phase was washed twice with EtOAc. The combined organic layers were dried over sodium sulphate.

Aufarbeitung

  1. customA slurry was formed
  2. additionwas added
  3. stirringThe mixture was shaken
  4. customthe organic layer collected
  5. washThe water phase was washed twice with EtOAc
  6. dry with materialThe combined organic layers were dried over sodium sulphate

Quellen und Nachweise

ORD-Eintrag
ord-8892e378c8674706a38778a51c6da2cb
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08143290B2

Verknüpfte Notizen

Wird geladen…