Chloroacetyl chloride → HCID 86646042, compound

HRID 1800600Notes

Reaction equation

HRID 1800600 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[CH:13]=[C:14]([NH:19][C:20](=[O:32])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:29])[CH3:28])[CH:22]=3)[CH:15]=[CH:16][C:17]=1[CH3:18])[N:5]=2.[Cl:33][CH2:34][C:35](Cl)=[O:36].C(=O)([O-])O.[Na+].C(N(CC)CC)C.[OH:50][CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1.[ClH:59].C(OCC)(=O)C>CN(C)C(=O)C.O>[ClH:33].[ClH:59].[ClH:33].[C:30]([C:27]([C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[C:20]([NH:19][C:14]1[CH:15]=[CH:16][C:17]([CH3:18])=[C:12]([O:11][C:6]2[N:5]=[C:4]3[S:3][C:2]([NH:1][C:35](=[O:36])[CH2:34][N:56]4[CH2:57][CH2:58][N:53]([CH2:52][CH2:51][OH:50])[CH2:54][CH2:55]4)=[N:10][C:9]3=[CH:8][CH:7]=2)[CH:13]=1)=[O:32])([CH3:29])[CH3:28])#[N:31]

Participants

9

Reactant 6

HCID 6577Chloroacetyl chlorideHCID 76771-(2-Hydroxyethyl)piperazineHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86646043HCID 86646043, compound

Product 1

HCID 86646042HCID 86646042, compoundYield 64.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (200 mg, 0.450 mmol) produced in Example C12(iv) in N,N-dimethylacetamide (3 mL) was added chloroacetyl chloride (68.6 μL, 0.863 mmol), and the mixture was stirred at room temperature for 3 hr. To the reaction mixture was added aqueous sodium hydrogen carbonate solution (5 mL), and the mixture was extracted with ethyl acetate (5 mL×3). The organic layers were combined, and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (3 mL), triethylamine (0.2 mL, 1.43 mmol) and 1-(2-hydroxyethyl)piperazine (160 μL, 1.30 mmol) were added, and the mixture was stirred at 60° C. for 14 hr. To the reaction mixture was added water (5 mL), and the mixture was extracted with ethyl acetate (5 mL×4). The organic layers were combined was washed successively with water (3 mL) and saturated brine (3 mL), and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/80→0/100), and fractions containing the object product were concentrated under reduced pressure. The residue was dissolved in ethyl acetate (3 mL), 4N hydrochloric acid/ethyl acetate (0.3 mL, 1.20 mmol) was added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated under reduced pressure to give the title compound (200 mg, 61%) as a white amorphous.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (5 mL×3)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in tetrahydrofuran (3 mL)
  5. stirringthe mixture was stirred at 60° C. for 14 hr
  6. extractionthe mixture was extracted with ethyl acetate (5 mL×4)
  7. washThe organic layers were combined was washed successively with water (3 mL) and saturated brine (3 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/80→0/100), and fractions
  11. additioncontaining the object product
  12. concentrationwere concentrated under reduced pressure
  13. dissolutionThe residue was dissolved in ethyl acetate (3 mL)
  14. stirringthe mixture was stirred at room temperature for 3 hr
  15. concentrationThe reaction mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-95e934f13c4a4cdbbc9b74a26b6d2c55
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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