Water → N-[5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1,1-dimethylprop-2-yn-1-yl)benzamide

HRID 1800560노트

반응식

HRID 1800560 반응식
[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].CN(C)C=O.[NH2:20][C:21]1[CH:22]=[C:23]([CH:40]=[CH:41][C:42]=1[F:43])[O:24][C:25]1[N:30]=[C:29]2[S:31][C:32]([NH:34][C:35]([CH:37]3[CH2:39][CH2:38]3)=[O:36])=[N:33][C:28]2=[CH:27][CH:26]=1.O>C(Cl)(=O)C(Cl)=O.CN(C)C(=O)C>[CH:37]1([C:35]([NH:34][C:32]2[S:31][C:29]3[C:28]([N:33]=2)=[CH:27][CH:26]=[C:25]([O:24][C:23]2[CH:40]=[CH:41][C:42]([F:43])=[C:21]([NH:20][C:9](=[O:11])[C:8]4[CH:12]=[CH:13][CH:14]=[C:6]([C:2]([CH3:1])([CH3:5])[C:3]#[CH:4])[CH:7]=4)[CH:22]=2)[N:30]=3)=[O:36])[CH2:38][CH2:39]1

참가 물질

7

반응물 4

HCID 962WaterHCID 6228DimethylformamideHCID 862274143-(2-Methylbut-3-yn-2-yl)benzoic acidHCID 86646022N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

생성물 1

HCID 59506931N-[5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1,1-dimethylprop-2-yn-1-yl)benzamide수율 37%

시약·촉매·용매 2

HCID 31374Dimethylacetamide용매HCID 65578Oxalyl chloride용매

실험 절차

To a solution of 3-(1,1-dimethylprop-2-yn-1-yl)benzoic acid (0.10 g, 0.5 mmol) in oxalyl chloride (1 mL) was added N,N-dimethylformamide (40 μL), and the mixture was stirred at room temperature for 30 min, and concentrated to dryness under reduced pressure. This was dissolved in a mixed solution of N,N-dimethylacetamide (1 mL) and tetrahydrofuran (1 mL), and the solution was added dropwise to a solution of N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (0.12 g, 0.33 mmol) produced in Example C63(vi) in N,N-dimethylacetamide (1 mL) under ice-cooling. The reaction mixture was stirred at room temperature for 3 hr, and poured into water (100 mL), and the mixture was extracted with ethyl acetate (100 mL×2). The ethyl acetate layers were combined, and dried over anhydrous sodium sulfate. The 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/hexane=0/100→100/0), and recrystallized from methanol to give the title compound (62 mg, 37%) as colorless crystals.

후처리

  1. concentrationconcentrated to dryness under reduced pressure
  2. dissolutionThis was dissolved in a mixed solution of N,N-dimethylacetamide (1 mL) and tetrahydrofuran (1 mL)
  3. temperaturecooling
  4. stirringThe reaction mixture was stirred at room temperature for 3 hr
  5. extractionthe mixture was extracted with ethyl acetate (100 mL×2)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe insoluble material was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0)
  10. customrecrystallized from methanol

출처 및 근거

ORD 기록
ord-cf93a4b41c9441cf96a63d6d8e8c681d
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344135B2

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