Dimethylformamide → N-[4-chloro-5-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-fluorophenyl]-3-(1,1-dimethylprop-2-yn-1-yl)benzamide

HRID 455199ノート

反応式

HRID 455199 の反応式
[CH3:1][C:2]([C:6]1[CH:7]=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=O)([CH3:5])[C:3]#[CH:4].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:26][C:27]1[C:28]([F:52])=[CH:29][C:30]([Cl:51])=[C:31]([CH:50]=1)[O:32][C:33]1[CH:47]=[CH:46][C:36]2[N:37]=[C:38]([NH:40][C:41]([CH:43]3[CH2:45][CH2:44]3)=[O:42])[S:39][C:35]=2[C:34]=1[C:48]#[N:49]>O1CCCC1.C(OCC)(=O)C>[Cl:51][C:30]1[C:31]([O:32][C:33]2[CH:47]=[CH:46][C:36]3[N:37]=[C:38]([NH:40][C:41]([CH:43]4[CH2:45][CH2:44]4)=[O:42])[S:39][C:35]=3[C:34]=2[C:48]#[N:49])=[CH:50][C:27]([NH:26][C:9](=[O:11])[C:8]2[CH:12]=[CH:13][CH:14]=[C:6]([C:2]([CH3:1])([CH3:5])[C:3]#[CH:4])[CH:7]=2)=[C:28]([F:52])[CH:29]=1

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 862274143-(2-Methylbut-3-yn-2-yl)benzoic acidHCID 86644692N-[6-(5-amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

生成物 1

HCID 86644693N-[4-chloro-5-({7-cyano-2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-fluorophenyl]-3-(1,1-dimethylprop-2-yn-1-yl)benzamide収率 56.3%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 3-(1,1-dimethylprop-2-yn-1-yl)benzoic acid (62 mg, 0.330 mmol) in tetrahydrofuran (1 mL) were added oxalyl chloride (35 μL, 0.408 mmol) and N,N-dimethylformamide (5 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (1 mL). N-[6-(5-Amino-2-chloro-4-fluorophenoxy)-7-cyano-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (90 mg, 0.223 mmol) produced in Example 23(vi) was added to the solution, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate (15 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (7 mL) and saturated brine (7 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=20/80→80/20), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate to give the title compound (72 mg, 56%) as a white powder.

後処理

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in N,N-dimethylacetamide (1 mL)
  3. stirringthe mixture was stirred at room temperature for 1 hr
  4. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (7 mL) and saturated brine (7 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationInsoluble material was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=20/80→80/20)
  9. concentrationthe obtained solution was concentrated under reduced pressure
  10. customThe residue was crystallized from ethyl acetate

出典と根拠

ORDレコード
ord-3ae561983d924048934dfa5ffe104978
出典データセット
uspto-grants-2013_07
特許番号
US08497274B2

反応ノート

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