2-(Di-tert-butylphosphino)biphenyl → 2-{3-[(5-Methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-yl)amino]phenyl}-ethanesulfonic acid

HRID 2374955노트

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HRID 2374955 반응식
Cl.[CH3:2][C:3]1[N:4]=[C:5]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:6]2[C:11]=1[CH:10]=[N:9][C:8]([NH2:12])=[N:7]2.Br[C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][S:28]([OH:31])(=[O:30])=[O:29])[CH:23]=[CH:24][CH:25]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>O1CCOCC1.CO>[CH3:2][C:3]1[N:4]=[C:5]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:6]2[C:11]=1[CH:10]=[N:9][C:8]([NH:12][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27][S:28]([OH:31])(=[O:30])=[O:29])[CH:23]=[CH:24][CH:25]=1)=[N:7]2

참가 물질

7

반응물 4

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 688705435-Methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-amine hydrochlorideHCID 860042332-(3-Bromophenyl)ethanesulfonic acid

생성물 1

HCID 113618552-{3-[(5-Methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-yl)amino]phenyl}-ethanesulfonic acid수율 66.2%

시약·촉매·용매 2

HCID 887Methanol용매HCID 312751,4-Dioxane용매

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온도
160 °C

실험 절차

To a solution of 5-methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-amine hydrochloride (28 mg, 0.107 mmol) in 1,4-dioxane (0.8 mL) was added 2-(3-bromophenyl)ethanesulfonic acid (28.25 mg, 0.107 mmol), 2-(dit-butylphosphino)biphenyl (9.6 mg, 0.032 mmol), Tris(dibenzylidineacetone)-dipalladium (0) (9.8 mg, 0.011 mmol) and sodium t-butoxide (23.65 mg, 0.246 mmol). In a sealed reaction vessel, the mixture was heated with microwave radiation at 160° C. for 13 minutes. After cooling to room temperature, methanol (5 mL) and silica gel (1.0 g) were added to the reaction mixture, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to isocratic elution using ethyl acetate:hexanes (50:50) followed by ethyl acetate:methanol (80:20) using a Biotage silica gel cartridge (8.0 g). The appropriate fractions were combined and concentrated under reduced pressure to give 2-{3-[(5-methyl-7-phenylimidazo[5,1-f][1,2,4]triazin-2-yl)amino]phenyl}-ethanesulfonic acid (0.029 g) as a yellow solid. 1H NMR (DMSO-d6): δ9.73 (s, 1H), 9.23 (s, 1H), 8.42 (d, J=7.5 Hz, 2H), 7.74 (s, 1H), 7.63 (dd, J=7.70 Hz, 2H), 7.49-7.07 (m, 3H), 6.86 (d, J=7.3 Hz, 1H), 2.94-2.82 (m, 2H), 2.71-2.62 (m, 2H), 2.52 (s, 3H). MS m/z 410 (M+1).

후처리

  1. customIn a sealed reaction vessel
  2. temperatureAfter cooling to room temperature
  3. customfollowed by evaporation of the volatiles under reduced pressure
  4. washsubjected to isocratic elution
  5. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-ba03ae1658ae44b890df566ce94fbd58
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07462614B2

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