Dimethylformamide → 3-(1-cyano-1-methylethyl)-N-[4-methyl-3-({2-[(morpholin-4-ylacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl}amino)phenyl]benzamide

HRID 1800736Notes

Reaction equation

HRID 1800736 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[S:7][C:8]2[N:9]=[C:10]([NH:15][C:16]3[CH:17]=[C:18]([NH:23][C:24](=[O:36])[C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:33])[CH3:32])[CH:26]=4)[CH:19]=[CH:20][C:21]=3[CH3:22])[N:11]=[CH:12][C:13]=2[N:14]=1)=[O:4].CN(C)C=O.C(N(CC)CC)C.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1>O1CCCC1.O>[C:34]([C:31]([C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=1)[C:24]([NH:23][C:18]1[CH:19]=[CH:20][C:21]([CH3:22])=[C:16]([NH:15][C:10]2[N:11]=[CH:12][C:13]3[N:14]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:49]4[CH2:54][CH2:53][O:52][CH2:51][CH2:50]4)[S:7][C:8]=3[N:9]=2)[CH:17]=1)=[O:36])([CH3:32])[CH3:33])#[N:35]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8083MorpholineHCID 8471TriethylamineHCID 86646091N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino)-4-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 595070003-(1-cyano-1-methylethyl)-N-[4-methyl-3-({2-[(morpholin-4-ylacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl}amino)phenyl]benzamideYield 78.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-d]pyrimidin-5-yl}amino)-4-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide (152 mg, 292 μmol) in tetrahydrofuran (4 mL)/N,N-dimethylformamide (0.5 mL) were added triethylamine (121 μL, 876 μmol) and morpholine (76 μL, 876 μmol), and the mixture was stirred at 60° C. for 15 hr. To the reaction mixture was added water (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→97/3), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from tetrahydrofuran and hexane to give the title compound (131 mg, 78%) as colorless crystals.

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. customThe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→97/3)
  7. additionthe fractions containing the object product
  8. concentrationwere concentrated under reduced pressure
  9. customThe obtained residue was recrystallized from tetrahydrofuran and hexane

Sources & evidence

ORD record
ord-ee9f6793135c4a9e90e20225cfcc4ec2
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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