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1,2-Dichloroethane → Dihydropyridone indazole amide 13

HRID 734678
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HRID 734678 반응식
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][C:13](=[O:15])[NH:12][C:11]([CH3:16])=[C:10]2[C:17](O)=[O:18])=[CH:5][CH:4]=1.[NH2:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][N:27]=[C:26]2[CH3:32].C(Cl)CCl.CCN(CC)CC>CN(C=O)C.CCOC(C)=O.Cl>[CH3:16][C:11]1[NH:12][C:13](=[O:15])[CH2:14][CH:9]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:20])([F:21])[F:1])=[CH:8][CH:7]=2)[C:10]=1[C:17]([NH:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][N:27]=[C:26]2[CH3:32])=[O:18]
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참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 160998632-Methyl-6-oxo-4-(4-(trifluoromethyl)phenyl)-1,4,5,6-tetrahydropyridine-3-carboxylic acidHCID 178434299HCID 178434299, 화합물

생성물 1

HCID 178429233Dihydropyridone indazole amide 13수율 6%

시약·촉매·용매 3

HCID 313
Hydrochloric Acid
용매
HCID 6228Dimethylformamide용매
HCID 8857Ethyl Acetate용매

실험 절차

The product of Example 5, Step 2 (225 mg, 0.75 mmol, 1.00 equiv), 5-amino-3-methylindazole (110 mg, 0.75 mmol, 1.0 equiv), and EDC (172 mg, 0.90 mmol, 1.20 equiv) were suspended in 2.0 mL DMF. Et3N (0.125 mL, 0.90 mmol, 1.2 equiv) was added and the solution was stirred at room temperature for 18 hrs. The reaction mixture was diluted with EtOAc and 1N HCl. The phases were separated, and the organic phase was washed twice with 1N HCl, once with satd. NaHCO3, and once with satd. NaCl. The organic phase was dried over Na2SO4, filtered, and concentrated en vacuo. The residue was purified by flash chromatography (20-100% EtOAc in Hexanes) and further purified by reverse-phase HPLC (10-70% CH3CN/H2O—NH4OH to pH 10 over 20 minutes, retention time 11.74 min) to provide 18 mg (6%) of the title compound as a white solid. MS (ES+) m/e 429 [M+H]+

후처리

  1. customThe phases were separated
  2. washthe organic phase was washed twice with 1N HCl, once with satd
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated en vacuo
  6. customThe residue was purified by flash chromatography (20-100% EtOAc in Hexanes)
  7. customfurther purified by reverse-phase HPLC (10-70% CH3CN/H2O—NH4OH to pH 10 over 20 minutes, retention time 11.74 min)

출처 및 근거

ORD 기록
ord-886a75f79ad04808aff51f605bfd94f4
출처 데이터셋
uspto-grants-2009_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07592357B2

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