Sodium Azide → 1-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-6-(2H-tetrazol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-ol

HRID 2402401Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2402401
[OH:1][C:2]1([C:14]2[S:15][C:16]([C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([NH:26][C:27]4[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][N:28]=4)[N:20]=3)=[CH:17][N:18]=2)[CH2:11][CH2:10][CH2:9][C:8]2[CH:7]=[C:6]([C:12]#[N:13])[CH:5]=[CH:4][C:3]1=2.[N-:37]=[N+:38]=[N-:39].[Na+]>[Br-].[Zn+2].[Br-].CN(C=O)C>[CH3:25][C:23]1[CH:22]=[C:21]([NH:26][C:27]2[CH:32]=[C:31]([C:33]([F:35])([F:34])[F:36])[CH:30]=[CH:29][N:28]=2)[N:20]=[C:19]([C:16]2[S:15][C:14]([C:2]3([OH:1])[C:3]4[C:8](=[CH:7][C:6]([C:12]5[N:37]=[N:38][NH:39][N:13]=5)=[CH:5][CH:4]=4)[CH2:9][CH2:10][CH2:11]3)=[N:18][CH:17]=2)[CH:24]=1

Komponenten

5

Edukt 2

HCID 33557Sodium AzideHCID 710022385-Hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile

Produkt 1

HCID 710022391-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-6-(2H-tetrazol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-olAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 10421208Zinc bromideKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
125 °C

Versuchsvorschrift

To a microwave vial was added 5-hydroxy-5-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile (250 mg, 0.493 mmol), sodium azide (32.0 mg, 0.493 mmol), zinc bromide (111 mg, 0.493 mmol) and DMF (2463 μl). The tube was sealed and heated to 125° C. for 16 h. The reaction was cooled to rt and filtered, then purified by reverse phase HPLC using a C18 column with a solvent system containing MeCN and H2O modified with 0.1% TFA. Product containing fractions were lyophilyzed to give 1-(5-(4-methyl-6-((4-(trifluoromethyl)pyridin-2-yl)amino)pyridin-2-yl)thiazol-2-yl)-6-(2H-tetrazol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-ol (35 mg, 13%) as a white powder. MS ESI calcd for C26H21F3N8OS [M+H]+ 551, found 551. 1H NMR (600 MHz, dmso) δ 10.17 (s, 1H), 8.63 (s, 1H), 8.46 (d, J=4.8, 1H), 8.22 (s, 1H), 7.81 (s, 1H), 7.75 (d, J=7.8, 1H), 7.41 (d, J=8.1, 1H), 7.34 (s, 1H), 7.18 (d, J=4.0, 1H), 7.07 (s, 1H), 6.62 (s, 1H), 2.90 (d, J=4.3, 2H), 2.42-2.33 (m, 1H), 2.28 (s, 3H), 2.19-2.07 (m, 1H), 2.07-1.90 (m, 2H) ppm.

Aufarbeitung

  1. customThe tube was sealed
  2. temperatureThe reaction was cooled to rt
  3. filtrationfiltered
  4. custompurified by reverse phase HPLC
  5. additioncontaining MeCN and H2O
  6. additionProduct containing fractions

Quellen und Nachweise

ORD-Eintrag
ord-f18c89380f924c0395f7a18259b8b682
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08796310B2

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