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

HRID 58077노트

반응식

HRID 58077 반응식
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

참가 물질

7

반응물 3

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

생성물 2

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

시약·촉매·용매 2

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

반응 조건

온도
140 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ba0aa8d3d7494743920ba5e115f815b4
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434743B2

반응 노트

불러오는 중…