tert-Butanol → 7-{5-[1(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl}-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline

HRID 1521611ノート

反応式

HRID 1521611 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH:12]=[N:13][N:14]=[C:7]1[CH2:6][CH2:5]2.[CH:15]1([C:18]2[N:22]=[C:21]([C:23]3([C:26]4[CH:27]=[C:28](B(O)O)[CH:29]=[N:30][CH:31]=4)[CH2:25][CH2:24]3)[O:20][N:19]=2)[CH2:17][CH2:16]1.C(=O)([O-])[O-].[K+].[K+].C(O)(C)(C)C>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.O>[CH:15]1([C:18]2[N:22]=[C:21]([C:23]3([C:26]4[CH:27]=[C:28]([C:2]5[CH:3]=[C:4]6[C:9](=[CH:10][CH:11]=5)[N:8]5[CH:12]=[N:13][N:14]=[C:7]5[CH2:6][CH2:5]6)[CH:29]=[N:30][CH:31]=4)[CH2:25][CH2:24]3)[O:20][N:19]=2)[CH2:17][CH2:16]1

参加物

7

反応物 4

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 21543699HCID 21543699、化合物HCID 89961641[5-[1-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl]boronic acid

生成物 1

HCID 899615587-{5-[1(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)cyclopropyl]-3-pyridinyl}-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoline

試薬・触媒・溶媒 2

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

反応条件

温度
80 °C

実験手順

To a vial containing the title compound from Example 22 Step B (0.025 g, 0.100 mmol), the title compound from Example 72 Step C (0.027 g, 0.100 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (1.4 mg, 2.0 μmol), and potassium carbonate (0.041 g, 0.300 mmol) were added tert-butanol (1.1 mL) and water (0.14 mL). The vial 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 material 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 N HCl solution was added, and the resulting solution concentrated under reduced pressure to provide the title compound: LCMS m/z 397.02 [M+H]+; 1H NMR (500 MHz, CD3OD) δ 9.37 (s, 1H), 9.01 (s, 1H), 8.85 (s, 1H), 8.60 (s, 1H), 7.92-7.86 (m, 3H), 3.27-3.24 (m, 4H), 2.02-1.99 (m, 1H), 1.92-1.90 (m, 2H), 1.78-1.76 (m, 2H), 1.04-1.00 (m, 2H), 0.91-0.89 (m, 2H).

後処理

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

出典と根拠

ORDレコード
ord-a0e80ca5049349ae897677587364ed1b
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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