Water → 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide

HRID 626555노트

반응식

HRID 626555 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]([NH:28][C:29]([CH:31]3[CH2:36][CH2:35][N:34]([CH3:37])[CH2:33][CH2:32]3)=[O:30])[CH:23]=2)=[CH:17][CH:16]=1.O>ClCCCl.C1COCC1>[CH3:37][N:34]1[CH2:35][CH2:36][CH:31]([C:29]([NH:28][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)=[O:30])[CH2:32][CH2:33]1

참가 물질

7

반응물 4

HCID 962WaterHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90409884N-(4-((6-aminopyridin-3-yl)oxy)pyridin-2-yl)-1-methylpiperidine-4-carboxamide

생성물 1

HCID 862729771-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide수율 28%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 2,2,2-trimethylacetamide (0.042 g, 0.412 mmol) in DCE (2 mL) was treated with oxalyl chloride (0.036 mL, 0.412 mmol), stirred at RT for 0.5 h, then heated at 75° C. for 1 h. The mixture was cooled to RT, added to a mixture of Example A8 (0.09 g, 0.275 mmol) and TEA (0.1 mL) in THF (2 mL) and stirred at RT for 1.5 h. The mixture was treated with water, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The material was layered with EtOAc, allowed to stand overnight and the resulting solid collected via filtration to afford 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperidine-4-carboxamide (35 mg, 27%) as a peach-colored solid. 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.52 (s, 1H), 10.50 (s, 1H), 8.25 (d, J=2.9 Hz, 1H), 8.20 (d, J=5.7 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.65 (d, J=2.4 Hz, 1H), 6.73 (dd, J=5.7, 2.4 Hz, 1H), 2.77 (m, 2H), 2.38 (m, 1H), 2.13 (s, 3H), 1.82 (m, 2H), 1.66 (m, 2H), 1.55 (m, 2H), 1.22 (s, 9H); MS (ESI) m/z: 455.3 (M+H+).

후처리

  1. temperatureheated at 75° C. for 1 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT for 1.5 h
  4. extractionextracted with EtOAc (3×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. waitto stand overnight
  8. filtrationthe resulting solid collected via filtration

출처 및 근거

ORD 기록
ord-1b34db19087d44f9bbe173a039dd802c
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309224B2

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