Chloroacetyl chloride → HCID 25206348, compound

HRID 1800686Notes

Reaction equation

HRID 1800686 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[N:5]=[C:6]([N:11]([CH3:32])[C:12]3[CH:13]=[C:14]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=4)[CH:15]=[CH:16][CH:17]=3)[N:7]=[CH:8][C:9]=2[N:10]=1.Cl[CH2:34][C:35](Cl)=[O:36].C(=O)([O-])O.[Na+].C(N(CC)CC)C.[CH3:50][N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1>CN(C)C(=O)C>[C:29]([C:26]([C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([N:11]([CH3:32])[C:6]2[N:7]=[CH:8][C:9]3[N:10]=[C:2]([NH:1][C:35](=[O:36])[CH2:34][N:54]4[CH2:55][CH2:56][N:51]([CH3:50])[CH2:52][CH2:53]4)[S:3][C:4]=3[N:5]=2)[CH:13]=1)=[O:31])([CH3:27])[CH3:28])#[N:30]

Participants

7

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 516892Sodium Bicarbonate2×HCID 86646073HCID 86646073, compound

Product 1

HCID 25206348HCID 25206348, compoundYield 50.4%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)(methyl)amino]phenyl}-3-(1-cyano-1-methylethyl)benzamide (152 mg, 343 μmol) produced in Example D5(i) in N,N-dimethylacetamide (4 mL) was added chloroacetyl chloride (68 μL, 858 μmol), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (20 mL), and the mixture was extracted with ethyl acetate (20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 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 dissolved in tetrahydrofuran (4 mL), triethylamine (143 μL, 1.03 mmol) and 1-methylpiperazine (115 μL, 1.03 mmol) were added, and the mixture was stirred at 60° C. for 3 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (15 mL), and the mixture was extracted with ethyl acetate (20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 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 (ethyl acetate/methanol=100/0→96/4), and the fractions containing the object product were concentrated under reduced pressure. To the obtained residue were added diisopropyl ether and ethyl acetate and the precipitate was collected by filtration to give the title compound (101 mg, 50%) as a colorless amorphous solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe obtained residue was dissolved in tetrahydrofuran (4 mL)
  7. stirringthe mixture was stirred at 60° C. for 3 hr
  8. extractionthe mixture was extracted with ethyl acetate (20 mL, 5 mL)
  9. washThe combined organic layer was washed with saturated brine (5 mL)
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationThe insoluble material was filtered off
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→96/4)
  14. additionthe fractions containing the object product
  15. concentrationwere concentrated under reduced pressure
  16. additionTo the obtained residue were added diisopropyl ether and ethyl acetate
  17. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-2ce800470bba4534a2cd526c5215461a
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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