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 2402401노트

반응식

HRID 2402401 반응식
[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

참가 물질

5

반응물 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

생성물 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-ol수율 13%

시약·촉매·용매 2

HCID 10421208Zinc bromide촉매HCID 6228Dimethylformamide용매

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온도
125 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f18c89380f924c0395f7a18259b8b682
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796310B2

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