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

HRID 58078노트

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HRID 58078 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: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

참가 물질

7

반응물 3

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

생성물 2

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

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

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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), (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.

후처리

  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

출처 및 근거

ORD 기록
ord-5eae70f9cbb44cbcbe29c316c354d7fd
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434743B2

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