Hydrochloric Acid → HCID 66926091, compound

HRID 2170795Notes

Reaction equation

HRID 2170795 reaction equation
C([N-]C(C)C)(C)C.[Li+].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:20]=[C:19]([CH3:21])[N:18]([C:22]3[C:23](=[O:29])[CH2:24][CH2:25][C:26]=3[O:27]C)[N:17]=2)=[CH:12][CH:11]=1.[F:30][C:31]1[CH:32]=[CH:33][C:34]([CH:37]=O)=[N:35][CH:36]=1.Cl>O1CCCC1.CC(C)=O>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:20]=[C:19]([CH3:21])[N:18]([CH:22]3[C:23](=[O:29])/[C:24](=[CH:37]\[C:34]4[CH:33]=[CH:32][C:31]([F:30])=[CH:36][N:35]=4)/[CH2:25][C:26]3=[O:27])[N:17]=2)=[CH:12][CH:11]=1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:20]=[C:19]([CH3:21])[N:18]([CH:22]3[C:23](=[O:29])/[C:24](=[CH:37]/[C:34]4[CH:33]=[CH:32][C:31]([F:30])=[CH:36][N:35]=4)/[CH2:25][C:26]3=[O:27])[N:17]=2)=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 2724682Lithium diisopropylamideHCID 103516975-Fluoropyridine-2-carboxaldehydeHCID 66926128HCID 66926128, compound

Product 2

HCID 66926091HCID 66926091, compoundHCID 66926173HCID 66926173, compound

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of lithium diisopropylamide (1.8 M in tetrahydrofuran/heptane/ethylbenzene, 0.25 ml, 0.45 mmol) was added drop wise to a solution of 2-[3-(4-chloro-phenyl)-5-methyl-pyrazol-1-yl]-3-methoxy-cyclopent-2-enone (124 mg, 0.41 mmol) in anhydrous tetrahydrofuran (1 ml) at −78° C., under nitrogen, and allowed to stir at this temperature for 30 minutes. 5-Fluoro-pyridine-2-carbaldehyde (56 mg, 0.45 mmol) was then added drop wise and the reaction stirred at −78° C. for a further 30 minutes. The reaction was then allowed to warm to room temperature over 30 mins and quenched by the addition of 1 M hydrochloric acid (5 ml) and extracted with dichlormethane (3×10 ml) to give 186 mg of crude material. The crude material was dissolved in acetone (2 ml) and 2 M hydrochloric acid (2 ml) added. This solution was heated in the microwave (using “normal” absorbtion) for 1 h at 120° C. This solution was extracted with dichloromethane (2×10 ml) and the organics dried over magnesium sulfate and reduced in vacuo. The crude material was purified by reverse phase preparative HPLC (eluting with acetonitrile/water) to give 2-[3-(4-chloro-phenyl)-5-methyl-pyrazol-1-yl]-4-[1-(5-fluoro-pyridin-2-yl)-meth-(Z)-ylidene]-cyclopentane-1,3-dione (22 mg) and 2-[3-(4-chloro-phenyl)-5-methyl-pyrazol-1-yl]-4-[1-(5-fluoro-pyridin-2-yl)-meth-(E)-ylidene]-cyclopentane-1,3-dione (5 mg).

Workup

  1. stirringthe reaction stirred at −78° C. for a further 30 minutes
  2. customquenched by the addition of 1 M hydrochloric acid (5 ml)
  3. extractionextracted with dichlormethane (3×10 ml)
  4. customto give 186 mg of crude material
  5. temperatureThis solution was heated in the microwave (using “normal” absorbtion) for 1 h at 120° C
  6. extractionThis solution was extracted with dichloromethane (2×10 ml)
  7. dry with materialthe organics dried over magnesium sulfate
  8. customThe crude material was purified by reverse phase preparative HPLC (eluting with acetonitrile/water)

Sources & evidence

ORD record
ord-e093cc1b7dd04f5a81d03176abdaf27c
Source dataset
uspto-grants-2015_06
Patent number
US09051300B2

Reaction notes

Loading…