Sodium Bicarbonate → 4-(3,6-dimethoxypyridazin-4-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58077ノート

反応式

HRID 58077 の反応式
Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH3:15][O:16][C:17]1[N:18]=[N:19][C:20]([O:26][CH3:27])=[CH:21][C:22]=1B(O)O.[C:28]([O-:31])(O)=[O:29].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:28]([OH:31])([C:11]([F:14])([F:13])[F:12])=[O:29].[CH3:15][O:16][C:17]1[N:18]=[N:19][C:20]([O:26][CH3:27])=[CH:21][C:22]=1[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazoleHCID 467392923,6-Dimethoxypyridazine-4-boronic acid

生成物 2

HCID 6422Trifluoroacetic acidHCID 717368234-(3,6-dimethoxypyridazin-4-yl)-6-(trifluoromethyl)-1H-indazole収率 4%

試薬・触媒・溶媒 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
140 °C

実験手順

A vial was charged with a mixture of 4-bromo-6-(trifluoromethyl)-1H-indazole (0.15 g, 0.566 mmol), (3,6-dimethoxypyridazin-4-yl)boronic acid (0.135 g, 0.736 mmol) and PdCl2(dppf) (0.021 g, 0.028 mmol) in dioxane (10 mL) and aqueous saturated NaHCO3 (3 mL). The resulting light brown suspension was heated at 140° C. for 45 minutes in a microwave reactor. The reaction mixture was subsequently concentrated and the crude residue was purified by preparative HPLC, eluting with a gradient of 40-45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes. The volatiles were removed in vacuo to give a TFA salt of the title compound as a light brown solid (8 mg, 4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.97 (s, 3H), 4.03 (s, 3H), 7.42 (s, 1H), 7.55 (d, J=1.01 Hz, 1H), 8.05 (s, 1H), 8.14 (s, 1H), 13.74 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H11F3N4O2, 325.1. found 325.16.

後処理

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with a gradient of 40-45% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes
  4. customThe volatiles were removed in vacuo

出典と根拠

ORDレコード
ord-ba0aa8d3d7494743920ba5e115f815b4
出典データセット
uspto-grants-2016_09
特許番号
US09434743B2

反応ノート

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