Pyridine → 3,3-dimethyl-N-((5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide

HRID 1049319ノート

反応式

HRID 1049319 の反応式
[CH3:1][C:2]1([CH3:9])[CH2:5][CH:4]([C:6]([NH2:8])=[O:7])[CH2:3]1.C(Cl)(=O)[C:11](Cl)=[O:12].[CH3:16][N:17]1[CH:21]=[C:20]([C:22]2[N:27]=[CH:26][N:25]=[C:24]([O:28][C:29]3[CH:30]=[CH:31][C:32]([NH2:35])=[N:33][CH:34]=3)[CH:23]=2)[CH:19]=[N:18]1.N1C=CC=CC=1>O1CCOCC1.C(Cl)Cl>[CH3:1][C:2]1([CH3:9])[CH2:5][CH:4]([C:6]([NH:8][C:11](=[O:12])[NH:35][C:32]2[CH:31]=[CH:30][C:29]([O:28][C:24]3[CH:23]=[C:22]([C:20]4[CH:19]=[N:18][N:17]([CH3:16])[CH:21]=4)[N:27]=[CH:26][N:25]=3)=[CH:34][N:33]=2)=[O:7])[CH2:3]1

参加物

7

反応物 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 5229333,3-Dimethylcyclobutane-1-carboxamideHCID 904033665-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine

生成物 1

HCID 862674303,3-dimethyl-N-((5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide収率 50.4%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A solution of Example B1 (0.120 g, 0.944 mmol) in dioxane (10 mL) was treated with oxalyl chloride (0.120 g, 0.945 mmol), heated at 100° C. for 3 h, concentrated to dryness, dissolved in DCM (10 mL), added to a solution of 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine (0.120 g, 0.447 mmol) in DCM (10 mL) and pyridine (0.070 g, 0.885 mmol) and stirred at RT overnight. The mixture was concentrated to dryness treated with MeCN and the solid collected via filtration and dried to afford 3,3-dimethyl-N-((5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide (95 mg, 49%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.07 (s, 1H), 10.71 (s, 1H), 8.63 (s, 1H), 8.47 (s, 1H), 8.26 (d, J=2.8 Hz, 1H), 8.16 (s, 1H), 8.05 (d, J=9.0 Hz, 1H), 7.75 (dd, J=9.0, 2.8 Hz, 1H), 7.43 (s, 1H), 3.89 (s, 3H), 3.30 (m, 1H), 2.00 (m, 4H), 1.13 (s, 3H), 1.05 (s, 3H); MS (ESI) m/z: 422.2 (M+H+).

後処理

  1. concentrationconcentrated to dryness
  2. dissolutiondissolved in DCM (10 mL)
  3. concentrationThe mixture was concentrated to dryness
  4. additiontreated with MeCN
  5. filtrationthe solid collected via filtration
  6. customdried

出典と根拠

ORDレコード
ord-8896553c864b4b9aae904c820f4b0092
出典データセット
uspto-grants-2016_07
特許番号
US09382228B2

反応ノート

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