Pyridine → HCID 71008607, compound

HRID 2037198Notes

Reaction equation

HRID 2037198 reaction equation
C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.[N:14]1C=CC=CC=1.[NH2:20][C:21]1[N:26]=[CH:25][C:24]([C:27]2[N:32]=[CH:31][C:30]([C:33]3([C:37]4[N:41]=[C:40]([C:42]5[CH:43]=[N:44][N:45]([CH2:47][C:48]([CH3:53])([CH3:52])[C:49](O)=O)[CH:46]=5)[O:39][N:38]=4)[CH2:36][CH2:35][CH2:34]3)=[CH:29][CH:28]=2)=[CH:23][N:22]=1.O.[OH-].[Li+]>C(Cl)Cl.C([O-])(O)=O.[Na+].C(OCC)(=O)C.CO.O.C1COCC1>[NH2:20][C:21]1[N:22]=[CH:23][C:24]([C:27]2[N:32]=[CH:31][C:30]([C:33]3([C:37]4[N:41]=[C:40]([C:42]5[CH:43]=[N:44][N:45]([CH2:47][C:48]([CH3:53])([CH3:52])[C:49]#[N:14])[CH:46]=5)[O:39][N:38]=4)[CH2:36][CH2:35][CH2:34]3)=[CH:29][CH:28]=2)=[CH:25][N:26]=1

Participants

11

Reactant 4

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 168937Lithium hydroxide, monohydrateHCID 66824717HCID 66824717, compound

Product 1

HCID 71008607HCID 71008607, compoundYield 26.1%

Reagents, catalysts & solvents 6

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

TFAA (73 μL, 0.522 mmol) is treated with CH2Cl2 (1.0 mL) and pyridine (42.2 μL, 0.522 mmol) and cooled to 0° C. To this mixture is added a solution of Example 147 (48.0 mg, 0.104 mmol) in CH2Cl2 (0.5 mL) and the resulting mixture is warmed to room temperature and stirred for 1 hour. The reaction is then quenched by the addition of saturated NaHCO3 and stirred for 30 minutes. The mixture is diluted with CH2Cl2 and water and the layers separated. The aqueous layer is extracted again with CH2Cl2 and the combined organics are dried over Na2SO4, filtered, and concentrated. The crude residue is then treated with THF (1.0 mL), water (0.5 mL), methanol (0.2 mL), and lithium hydroxide monohydrate (8.6 mg, 0.21 mmol) and the resulting mixture is heated at 40° C. for 30 minutes. The mixture is then diluted with saturated NaHCO3 and ethyl acetate and the layers separated. The aqueous is then extracted with ethyl acetate again and the combined organics are dried over Na2SO4, filtered, and concentrated. The resulting residue is triturated with acetonitrile to give the title compound (12.0 mg).

Workup

  1. temperaturethe resulting mixture is warmed to room temperature
  2. customThe reaction is then quenched by the addition of saturated NaHCO3
  3. stirringstirred for 30 minutes
  4. additionThe mixture is diluted with CH2Cl2 and water
  5. customthe layers separated
  6. extractionThe aqueous layer is extracted again with CH2Cl2
  7. dry with materialthe combined organics are dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. temperaturethe resulting mixture is heated at 40° C. for 30 minutes
  11. customthe layers separated
  12. extractionThe aqueous is then extracted with ethyl acetate again
  13. dry with materialthe combined organics are dried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe resulting residue is triturated with acetonitrile

Sources & evidence

ORD record
ord-4d32895e385f4440b98ce0e42f8bb77a
Source dataset
uspto-grants-2013_11
Patent number
US08575201B2

Reaction notes

Loading…