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 2402401ノート

反応式

HRID 2402401 の反応式
[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

参加物

5

反応物 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

生成物 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-ol収率 13%

試薬・触媒・溶媒 2

HCID 10421208Zinc bromide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
125 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f18c89380f924c0395f7a18259b8b682
出典データセット
uspto-grants-2014_08
特許番号
US08796310B2

反応ノート

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