Dimethylacetamide → HCID 59507027, compound

HRID 1800530Notes

Reaction equation

HRID 1800530 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([O:11][C:12]1[C:13]([Cl:33])=[CH:14][C:15]([F:32])=[C:16]([NH:18][C:19](=[O:31])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=3)[CH:17]=1)[N:5]=2.CC(N(C)C)=O.[C:40]1(/[CH:46]=[CH:47]/[C:48](Cl)=[O:49])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:33][C:13]1[C:12]([O:11][C:6]2[N:5]=[C:4]3[S:3][C:2]([NH:1][C:48](=[O:49])/[CH:47]=[CH:46]/[C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[N:10][C:9]3=[CH:8][CH:7]=2)=[CH:17][C:16]([NH:18][C:19](=[O:31])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=2)=[C:15]([F:32])[CH:14]=1

Participants

6

Reactant 3

HCID 31374DimethylacetamideHCID 5354261Cinnamoyl ChlorideHCID 86646015N-(5-[(2-Amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 59507027HCID 59507027, compoundYield 86.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide (80 mg, 0.166 mmol) produced in Example C52(v) in pyridine (1.0 mL) were added dimethylacetamide (0.5 mL) and (2E)-3-phenylprop-2-enoyl chloride (55 mg, 0.332 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate (20 mL), washed with 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL), 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 basic silica gel column chromatography (hexane/ethyl acetate=70/30→0/100), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/hexane to give the title compound (87.5 mg, 86%) as a colorless powder.

Workup

  1. washwashed with 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationThe insoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=70/30→0/100)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was crystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-9ce56f862f9749ef8919f98da6ccbcf7
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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