Benzenesulfonic Acid → 4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-2-(4-(2-hydroxy-2-methylpropoxy)-2-fluoro-5-(4,5-dihydro-4-methyl-5-oxotetrazol-1-yl)phenylamino)pyrimidine-5-carbonitrile

HRID 1754441Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1754441
[NH2:1][C:2]1[C:3]([F:21])=[CH:4][C:5]([O:15][CH2:16][C:17]([OH:20])([CH3:19])[CH3:18])=[C:6]([N:8]2[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]2)[CH:7]=1.Cl[C:23]1[N:28]=[C:27]([NH:29][C@@H:30]2[CH2:38][C@H:37]3[N:33]([CH2:34][CH2:35][CH2:36]3)[C:32]([CH3:40])([CH3:39])[CH2:31]2)[C:26]([C:41]#[N:42])=[CH:25][N:24]=1.C1(S(O)(=O)=O)C=CC=CC=1>CC(O)C>[CH3:39][C:32]1([CH3:40])[CH2:31][C@H:30]([NH:29][C:27]2[C:26]([C:41]#[N:42])=[CH:25][N:24]=[C:23]([NH:1][C:2]3[CH:7]=[C:6]([N:8]4[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]4)[C:5]([O:15][CH2:16][C:17]([OH:20])([CH3:19])[CH3:18])=[CH:4][C:3]=3[F:21])[N:28]=2)[CH2:38][C@H:37]2[N:33]1[CH2:34][CH2:35][CH2:36]2

Komponenten

5

Edukt 3

HCID 7371Benzenesulfonic AcidHCID 86704483(7R,8aS)-N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amineHCID 867044841-(5-amino-2-(2-hydroxy-2-methylpropoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one

Produkt 1

HCID 718115594-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-2-(4-(2-hydroxy-2-methylpropoxy)-2-fluoro-5-(4,5-dihydro-4-methyl-5-oxotetrazol-1-yl)phenylamino)pyrimidine-5-carbonitrileAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of 1-(5-amino-2-(2-hydroxy-2-methylpropoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one (305 mg), (7R,8aS)—N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (262 mg), and benzenesulfonic acid (160 mg) in IPA (2 mL) were heated to 80° C. overnight. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The crude product was absorbed onto silica gel and purified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-30%) to give desired product (386 mg, 80%).

Aufarbeitung

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe crude mixture was concentrated to dryness
  3. customThe crude product was absorbed onto silica gel
  4. custompurified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-30%)

Quellen und Nachweise

ORD-Eintrag
ord-80b979e4ecf443af89db251fc0077a86
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169249B2

Notizen zur Reaktion

Wird geladen…