Potassium Carbonate → 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)-1H-imidazole-4-carboxamide

HRID 626566

반응식

HRID 626566 반응식
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[CH3:25][N:26]1[CH:30]=[C:29]([C:31](O)=[O:32])[N:28]=[CH:27]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:25][N:26]1[CH:30]=[C:29]([C:31]([NH:1][C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:14]=[N:13][C:12]([NH:15][C:16]([NH:18][C:19](=[O:24])[C:20]([CH3:21])([CH3:23])[CH3:22])=[O:17])=[CH:11][CH:10]=3)[CH:5]=[CH:4][N:3]=2)=[O:32])[N:28]=[CH:27]1

참가 물질

7

반응물 5

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 5415091-methyl-1H-imidazole-4-carboxylic acid2회HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2회HCID 90409811N-((5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

생성물 1

HCID 862744261-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)-1H-imidazole-4-carboxamide수율 26.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
60 °C

실험 절차

A mixture of Example C1 (0.15 g, 0.455 mmol), 1-methyl-1H-imidazole-4-carboxylic acid (0.172 g, 1.366 mmol), TBTU (0.439 g, 1.366 mmol) and DIEA (0.476 mL, 2.73 mmol) in DMF (5 mL) was stirred at RT for 2 h, then heated at 60° C. overnight. Additional 1-methyl-1H-imidazole-4-carboxylic acid (0.172 g, 1.366 mmol) and TBTU (0.439 g, 1.366 mmol) were added and the mixture heated at 60° C. overnight. The mixture was cooled to RT, treated with 10% K2CO3, extracted with DCM (4×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The material was further purified via preparative TLC (MeOH/DCM) to afford 1-methyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)-1H-imidazole-4-carboxamide (52 mg, 26%). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.47 (s, 1H), 8.29 (d, J=2.9 Hz, 1H), 8.22 (d, J=5.8 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.85 (d, J=1.2 Hz, 1H), 7.78-7.77 (m, 2H), 7.75 (d, J=2.4 Hz, 1H), 6.75 (dd, J=5.8, 2.4 Hz, 1H), 3.71 (s, 3H), 1.22 (s, 9H); MS (ESI) m/z: 438.2 (M+H+).

후처리

  1. temperaturethe mixture heated at 60° C. overnight
  2. temperatureThe mixture was cooled to RT
  3. extractionextracted with DCM (4×)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to dryness
  7. custompurified via silica gel chromatography (MeOH/DCM)
  8. customThe material was further purified via preparative TLC (MeOH/DCM)

출처 및 근거

ORD 기록
ord-bb0b79e06b9342cfb1041e92ca9b105e
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309224B2

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