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

HRID 1049314노트

반응식

HRID 1049314 반응식
[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[CH:27]=[C:26]([O:28][C:29]3[CH:30]=[CH:31][C:32]([NH2:35])=[N:33][CH:34]=3)[CH:25]=[CH:24][N:23]=2)[CH:19]=[N:18]1.N1C=CC=CC=1>ClCCCl.C1COCC1>[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:26]3[CH:25]=[CH:24][N:23]=[C:22]([C:20]4[CH:19]=[N:18][N:17]([CH3:16])[CH:21]=4)[CH:27]=3)=[CH:34][N:33]=2)=[O:7])[CH2:3]1

참가 물질

7

반응물 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 5229333,3-Dimethylcyclobutane-1-carboxamideHCID 593227775-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)pyridin-2-amine

생성물 1

HCID 862674323,3-dimethyl-N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide수율 61.2%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 8028Tetrahydrofuran용매

실험 절차

A suspension of Example B1 (0.074 g, 0.584 mmol) in DCE (6 mL) was treated with oxalyl chloride (0.051 mL, 0.584 mmol), stirred at RT for 30 min, then warmed to 83° C. for 3 h. The mixture was cooled to RT and added drop-wise to a solution of Example A2 (0.13 g, 0.486 mmol) in THF (6.0 mL) and pyridine (0.197 mL, 2.43 mmol). The mixture was stirred at RT for 1 h, treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over MgSO4 and concentrated to dryness. The residue was triturated with MeCN, sonicated for 5 min and the solid was collected via filtration and dried to afford 3,3-dimethyl-N-((5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclobutanecarboxamide (125 mg, 61%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 10.70 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27-8.25 (m, 2H), 8.07 (d, J=9.0 Hz, 1H), 7.96 (d, J=0.7 Hz, 1H), 7.72 (dd, J=9.0, 2.9 Hz, 1H), 7.23 (d, J=2.4 Hz, 1H), 6.70 (dd, J=5.7, 2.4 Hz, 1H), 3.84 (s, 3H), 3.24 (m, 1H), 2.03-1.87 (m, 4H), 1.13 (s, 3H), 1.05 (s, 3H); MS (ESI) m/z: 421.2 (M+H+).

후처리

  1. temperaturewarmed to 83° C. for 3 h
  2. temperatureThe mixture was cooled to RT
  3. stirringThe mixture was stirred at RT for 1 h
  4. additiontreated with satd
  5. extractionNaHCO3, extracted with EtOAc (3×)
  6. dry with materialthe combined organics were dried over MgSO4
  7. concentrationconcentrated to dryness
  8. customThe residue was triturated with MeCN
  9. customsonicated for 5 min
  10. filtrationthe solid was collected via filtration
  11. customdried

출처 및 근거

ORD 기록
ord-9db534a3fbef437591f979c899994428
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09382228B2

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