Morpholine → N-[4-chloro-2-fluoro-5-({2-[(morpholin-4-ylacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethyl)benzamide

HRID 1800528Notes

Reaction equation

HRID 1800528 reaction equation
[Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[C:13]3[S:15][C:16]([NH:18][C:19](=[O:22])[CH2:20]Cl)=[N:17][C:12]3=[CH:11][CH:10]=2)=[CH:6][C:5]([NH:23][C:24](=[O:36])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:33])[CH3:32])[CH:26]=2)=[C:4]([F:37])[CH:3]=1.C(N(CC)CC)C.[NH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[C:13]3[S:15][C:16]([NH:18][C:19](=[O:22])[CH2:20][N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[N:17][C:12]3=[CH:11][CH:10]=2)=[CH:6][C:5]([NH:23][C:24](=[O:36])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:32])[CH3:33])[CH:26]=2)=[C:4]([F:37])[CH:3]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 8471TriethylamineHCID 86646016N-[4-chloro-5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 59507019N-[4-chloro-2-fluoro-5-({2-[(morpholin-4-ylacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethyl)benzamideYield 80%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

N-[4-Chloro-5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide synthesized above was dissolved in tetrahydrofuran (3.0 mL), triethylamine (85.6 μL, 0.621 mmol) and morpholine(54.3 μL, 0.621 mmol) were added, and the mixture was stirred at 80° C. for 8 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), washed with water (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 residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→85/15), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/hexane to give the title compound (101 mg, 80%) as a colorless amorphous powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (10 mL) and saturated brine (10 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 residue was purified by basic silica gel column chromatography (ethyl acetate/methanol=100/0→85/15)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was triturated with ethyl acetate/hexane

Sources & evidence

ORD record
ord-20d118f9d4264787b4a4809e7e5acb22
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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