Sodium Bicarbonate → 4-(6-methoxy-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58078ノート

反応式

HRID 58078 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:22]=[C:21]([CH3:23])[C:20](B(O)O)=[CH:19][CH:18]=1.[C:27]([O-:30])(O)=[O:28].[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:27]([OH:30])([C:11]([F:14])([F:13])[F:12])=[O:28].[CH3:15][O:16][C:17]1[N:22]=[C:21]([CH3:23])[C:20]([C:2]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]3[C:3]=2[CH:4]=[N:5][NH:6]3)=[CH:19][CH:18]=1

参加物

7

反応物 3

HCID 516892Sodium BicarbonateHCID 27630842-Methyl-6-methoxypyridine-3-boronic acidHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazole

生成物 2

HCID 6422Trifluoroacetic acidHCID 897832044-(6-methoxy-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole収率 47%

試薬・触媒・溶媒 2

HCID 178418228Bis(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), (6-methoxy-2-methylpyridin-3-yl)boronic acid (0.123 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 microwave reactor. The reaction mixture was subsequently concentrated and the crude residue was purified by preparative HPLC, eluting with 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 oil (82 mg, 47%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.30 (s, 3H), 3.93 (s, 3H), 6.75-6.86 (m, 1H), 7.29 (d, J=1.26 Hz, 1H), 7.72 (d, J=8.34 Hz, 1H), 7.90-8.03 (m, 2H); ESI-MS m/z [M+H]+ calc'd for C15H12F3N3O, 308.1. found 308.15.

後処理

  1. concentrationThe reaction mixture was subsequently concentrated
  2. customthe crude residue was purified by preparative HPLC
  3. washeluting with 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-5eae70f9cbb44cbcbe29c316c354d7fd
出典データセット
uspto-grants-2016_09
特許番号
US09434743B2

反応ノート

読み込み中…