Trimethylacetamide → HCID 86274907、化合物

HRID 626588ノート

反応式

HRID 626588 の反応式
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[NH2:14][C:15]1[N:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]([C:28]([NH:30][CH:31]3[CH2:33][CH2:32]3)=[O:29])[CH:23]=2)=[CH:17][CH:16]=1.CCN(C(C)C)C(C)C>ClCCCl.O1CCOCC1.CCOC(C)=O>[CH:31]1([NH:30][C:28](=[O:29])[C:24]2[CH:23]=[C:22]([O:21][C:18]3[CH:19]=[N:20][C:15]([NH:14][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])=[CH:16][CH:17]=3)[CH:27]=[CH:26][N:25]=2)[CH2:32][CH2:33]1

参加物

8

反応物 4

HCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 90411099HCID 90411099、化合物

生成物 1

HCID 86274907HCID 86274907、化合物収率 67%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A suspension of 2,2,2-trimethylacetamide (0.150 g, 1.480 mmol) in DCE (4 mL) was treated with oxalyl chloride (0.130 mL, 1.480 mmol), heated at 80° C. for 1 h, cooled to RT, added drop-wise to a solution of 4-((6-aminopyridin-3-yl)oxy)-N-cyclopropylpicolinamide (0.2 g, 0.740 mmol) and DIEA (0.646 mL, 3.70 mmol) in dioxane (4 mL) and stirred at RT for 20 h. The mixture was diluted with EtOAc, washed with satd. NaHCO3, water, then brine and the combined aqueous washes were back-extracted with EtOAc. The combined organics were dried over Na2SO4, concentrated to dryness and purified by silica gel chromatography (EtOAc/DCM) to afford N-cyclopropyl-4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)picolinamide (0.196 g, 67%). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.46 (s, 1H), 8.75 (d, J=5.1 Hz, 1H), 8.50 (d, J=5.6 Hz, 1H), 8.30 (d, J=2.9 Hz, 1H), 8.11 (d, J=9.0 Hz, 1H), 7.78 (dd, J=9.0, 2.9 Hz, 1H), 7.40 (d, J=2.6 Hz, 1H), 7.19 (dd, J=5.6, 2.6 Hz, 1H), 2.87-2.85 (m, 1H), 1.21 (s, 9H), 0.65 (d, J=8.0 Hz, 4H); MS (ESI) m/z: 398.2 (M+H+).

後処理

  1. temperaturecooled to RT
  2. washwashed with satd
  3. extractionNaHCO3, water, then brine and the combined aqueous washes were back-extracted with EtOAc
  4. dry with materialThe combined organics were dried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified by silica gel chromatography (EtOAc/DCM)

出典と根拠

ORDレコード
ord-1fffef1dc21f40f9ab0f63e77650c682
出典データセット
uspto-grants-2016_04
特許番号
US09309224B2

反応ノート

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