Potassium Carbonate → 2-[5-(4,5-Dihydro[1,2,4]triazolo[4,3-a]quinolin-7-yl)pyridin-3-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol

HRID 1521591ノート

反応式

HRID 1521591 の反応式
[F:1][C:2]([F:19])([F:18])[C:3]([C:9]1[CH:10]=[C:11](B(O)O)[CH:12]=[N:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].Br[C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]1[CH:31]=[N:32][N:33]=[C:26]1[CH2:25][CH2:24]2.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)(C)C.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH:31]1[N:27]2[C:28]3[C:23]([CH2:24][CH2:25][C:26]2=[N:33][N:32]=1)=[CH:22][C:21]([C:11]1[CH:10]=[C:9]([C:3]([OH:8])([C:4]([F:7])([F:6])[F:5])[C:2]([F:19])([F:18])[F:1])[CH:14]=[N:13][CH:12]=1)=[CH:30][CH:29]=3

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 21543699HCID 21543699、化合物HCID 89961718(5-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)pyridin-3-yl)boronic acid

生成物 1

HCID 899615962-[5-(4,5-Dihydro[1,2,4]triazolo[4,3-a]quinolin-7-yl)pyridin-3-yl]-1,1,1,3,3,3-hexafluoropropan-2-ol

試薬・触媒・溶媒 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 962Water溶媒HCID 6386tert-Butanol溶媒

反応条件

温度
80 °C

実験手順

A vial containing the title compound from Example 61 Step B (15 mg, 0.05 mmol), the title compound from Example 22 Step B (11.7 mg, 0.047 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (3.68 mg, 5.19 μmol) and potassium carbonate (21.5 mg, 0.156 mmol) in tert-butanol (577 μL) and water (72 μL) was flushed with nitrogen, sealed tightly and heated to 80° C. overnight. The reaction solution was then cooled to room temperature and concentrated under reduced pressure. The resulting residue was diluted with acetonitrile and purified by HPLC (C18 column, 10 to 100% acetonitrile/water, both 0.1% v/v trifluoroacetic acid). Fractions containing product were combined, aqueous 1 M hydrochloric acid solution was added and the solution concentrated under reduced pressure to provide the title compound: LCMS m/z 414.79 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 9.38 (s, 1H), 9.11 (s, 1H), 8.85 (s, 1H), 8.27 (s, 1H), 7.92 (d, J=8.34 Hz, 1H) 7.87 (d, J=1.71 Hz, 1H), 7.81 (dd, J=1.94, 8.34 Hz, 1H), 3.15 (s, 4H).

後処理

  1. customsealed tightly
  2. temperatureThe reaction solution was then cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. additionThe resulting residue was diluted with acetonitrile
  5. custompurified by HPLC (C18 column, 10 to 100% acetonitrile/water
  6. additionFractions containing product
  7. additionaqueous 1 M hydrochloric acid solution was added
  8. concentrationthe solution concentrated under reduced pressure

出典と根拠

ORDレコード
ord-1a4d51e581f944aa864ef31b0d3c155c
出典データセット
uspto-grants-2015_07
特許番号
US09073929B2

反応ノート

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