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

HRID 1800550노트

반응식

HRID 1800550 반응식
[Cl:1][C:2]1[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C)C=O.[NH2:21][C:22]1[CH:23]=[C:24]([CH:41]=[CH:42][C:43]=1[F:44])[O:25][C:26]1[N:31]=[C:30]2[S:32][C:33]([NH:35][C:36]([CH:38]3[CH2:40][CH2:39]3)=[O:37])=[N:34][C:29]2=[CH:28][CH:27]=1.O>C(Cl)(=O)C(Cl)=O.CN(C)C(=O)C>[Cl:1][C:2]1[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:21][C:22]1[CH:23]=[C:24]([O:25][C:26]2[N:31]=[C:30]3[S:32][C:33]([NH:35][C:36]([CH:38]4[CH2:40][CH2:39]4)=[O:37])=[N:34][C:29]3=[CH:28][CH:27]=2)[CH:41]=[CH:42][C:43]=1[F:44])=[O:6]

참가 물질

7

반응물 4

HCID 962WaterHCID 6228DimethylformamideHCID 668102752-Chloro-3-(1-cyano-1-methylethyl)benzoic acidHCID 86646022N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

생성물 1

HCID 252061832-chloro-3-(1-cyano-1-methylethyl)-N-[5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]benzamide수율 78.2%

시약·촉매·용매 2

HCID 31374Dimethylacetamide용매HCID 65578Oxalyl chloride용매

실험 절차

To a solution of 2-chloro-3-(1-cyano-1-methylethyl)benzoic acid (0.33 g, 1.5 mmol) produced in Example C61(v) in oxalyl chloride (1.5 mL) was added N,N-dimethylformamide (100 μL), and the mixture was stirred at room temperature for 30 min, and concentrated to dryness under reduced pressure. This was dissolved in a mixture of N,N-dimethylacetamide (1.5 mL) and tetrahydrofuran (1.5 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 (0.345 g, 1.00 mmol) in N,N-dimethylacetamide (3 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 (430 mg, 78%) as colorless crystals.

후처리

  1. concentrationconcentrated to dryness under reduced pressure
  2. dissolutionThis was dissolved in a mixture of N,N-dimethylacetamide (1.5 mL) and tetrahydrofuran (1.5 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-df0af324f67641e894afd2f43f21223f
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08344135B2

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