1,2-Dichloroethane → (E)-2-[2-(1H-indazol-3-yl)vinyl]-N-(thiazol-2-yl)benzamide

HRID 1821343ノート

反応式

HRID 1821343 の反応式
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14]([OH:16])=O)=[N:2]1.CN1CCOCC1.[NH2:28][C:29]1[S:30][CH:31]=[CH:32][N:33]=1.C(Cl)CCl.O.ON1C2C=CC=CC=2N=N1>C1COCC1.C(OCC)(=O)C.O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14]([NH:28][C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[O:16])=[N:2]1

参加物

9

反応物 5

HCID 111,2-DichloroethaneHCID 21552-AminothiazoleHCID 79724-MethylmorpholineHCID 27960291-Hydroxybenzotriazole hydrateHCID 57586985(E)-2-[2-(1H-indazol-3-yl)vinyl]benzoic acid

生成物 1

HCID 86628202(E)-2-[2-(1H-indazol-3-yl)vinyl]-N-(thiazol-2-yl)benzamide収率 22.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of (E)-2-[2-(1H-indazol-3-yl)vinyl]benzoic acid (30 mg, 0.11 mmol) obtained in Step 1 of Example 47 in THF (0.50 mL), was sequentially added with 4-methylmorpholine (25 μL, 0.23 mmol), 2-aminothiazole (17 mg, 0.17 mmol), EDC (31 mg, 0.16 mmol) and 1-hydroxybenzotriazole monohydrate (20 mg, 0.15 mmol), followed by stirring at room temperature for 2.0 hours. The reaction mixture was added with water and ethyl acetate to separate the mixture into organic layer and aqueous layer and the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 95/5) and the obtained compound was crystallized from 4.0 mol/L hydrogen chloride-ethyl acetate solution (1.0 mL)/ethyl acetate (1.0 mL). The obtained solid was added with ethyl acetate and saturated aqueous sodium hydrogencarbonate solution to separate the mixture into organic layer and aqueous layer and the organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=15/1) to obtain Compound 138 (8.5 mg, 22%).

後処理

  1. customto separate the mixture into organic layer and aqueous layer
  2. concentrationthe organic layer was concentrated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/0 to 95/5)
  4. customthe obtained compound was crystallized from 4.0 mol/L hydrogen chloride-ethyl acetate solution (1.0 mL)/ethyl acetate (1.0 mL)
  5. additionThe obtained solid was added with ethyl acetate and saturated aqueous sodium hydrogencarbonate solution
  6. customto separate the mixture into organic layer and aqueous layer
  7. concentrationthe organic layer was concentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (chloroform/methanol=15/1)

出典と根拠

ORDレコード
ord-c17cfcb458f64facbc4b6d1771ca80ba
出典データセット
uspto-grants-2009_10
特許番号
US07605272B2

反応ノート

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