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

HRID 1800566
Notes
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Reaction equation

HRID 1800566 reaction equation
[Cl:1][C:2]1[C:10]([O:11][C:12]([C:15]#[N:16])([CH3:14])[CH3:13])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C)C=O.[NH2:22][C:23]1[CH:24]=[C:25]([CH:40]=[CH:41][C:42]=1[F:43])[O:26][C:27]1[N:32]=[C:31]2[S:33][C:34]([NH:36][C:37](=[O:39])[CH3:38])=[N:35][C:30]2=[CH:29][CH:28]=1.O>C(Cl)(=O)C(Cl)=O.CN(C)C(=O)C>[C:37]([NH:36][C:34]1[S:33][C:31]2[C:30]([N:35]=1)=[CH:29][CH:28]=[C:27]([O:26][C:25]1[CH:40]=[CH:41][C:42]([F:43])=[C:23]([NH:22][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[C:10]([O:11][C:12]([C:15]#[N:16])([CH3:14])[CH3:13])[C:2]=3[Cl:1])[CH:24]=1)[N:32]=2)(=[O:39])[CH3:38]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 684177462-Chloro-3-(1-cyano-1-methylethoxy)benzoic acidHCID 86646025N-(5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]acetamide

Product 1

HCID 59507050N-(5-{[2-(acetylamino)[1,3]thiazolo[5,4-b]pyridin-5-yl]oxy}-2-fluorophenyl)-2-chloro-3-(1-cyano-1-methylethoxy)benzamide
Yield 14%

Reagents, catalysts & solvents 2

HCID 31374DimethylacetamideSolventHCID 65578Oxalyl chlorideSolvent

Procedure

To a solution of 2-chloro-3-(1-cyano-1-methylethoxy)benzoic acid (0.12 g, 0.5 mmol) in oxalyl chloride (0.5 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 mixture of N,N-dimethylacetamide (1 mL) and tetrahydrofuran (1 mL), and a solution was added dropwise to a solution of N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]acetamide (0.11 g, 0.33 mmol) produced in Example C64(ii) 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 (24 mg, 14%) as colorless crystals.

Workup

  1. concentrationconcentrated to dryness under reduced pressure
  2. dissolutionThis was dissolved in a mixture 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

Sources & evidence

ORD record
ord-233fb980c94e4cd0bec1a45dd9ca26a0
Source dataset
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08344135B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes