Trimethylacetamide → HCID 86274907, 화합물

HRID 626588노트

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HRID 626588 반응식
[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

참가 물질

8

반응물 4

HCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 90411099HCID 90411099, 화합물

생성물 1

HCID 86274907HCID 86274907, 화합물수율 67%

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-1fffef1dc21f40f9ab0f63e77650c682
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309224B2

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