Sodium hydride → HCID 11692553, compound

HRID 1786060Notes

Reaction equation

HRID 1786060 reaction equation
C[O:2][C:3](=O)[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([N:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C@H:19]([N:26]([C:34](=[O:36])[CH3:35])[C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)[CH2:18][C@@H:17]2[CH3:37])=[O:15])=[CH:10][CH:9]=1.[C:39](=[N:42]O)([NH2:41])[CH3:40].[H-].[Na+]>C1COCC1>[Cl:33][C:30]1[CH:29]=[CH:28][C:27]([N:26]([C@H:19]2[C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:16]([C:14](=[O:15])[C:11]3[CH:10]=[CH:9][C:8]([O:7][CH2:6][CH2:5][CH2:4][C:3]4[O:2][N:42]=[C:39]([CH3:40])[N:41]=4)=[CH:13][CH:12]=3)[C@@H:17]([CH3:37])[CH2:18]2)[C:34](=[O:36])[CH3:35])=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 30926N-HydroxyacetamidineHCID 68923892HCID 68923892, compound2×

Product 1

HCID 11692553HCID 11692553, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2S,4R)-N-(4-Chloro-phenyl)-N-(2-methyl-1-{4-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-propoxy]-benzoyl}-1,2,3,4-tetrahydro-quinolin-4-yl)-acetamide was prepared from (2S,4R)-4-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid methyl ester. Acetamide oxime (0.043 g, 0.58 mmol) was suspended in THF under N2 and NaH (60% dispersion in oil) (0.025 g, 1.0 mmol) was added followed by 4A° molecular sieves and heated to 60° C. for 1 h. (2S,4R)-4-(4-{4-[acetyl(4-chloro-phenyl)-amino]-2-methyl-3,4-dihydro-2H-quinoline-1-carbonyl}-phenoxy)-butyric acid methyl ester was added and heated to reflux for 4.5 h. The reaction was filtered and concentrated down and partitioned between CH2Cl2 and water. The aqueous layer was extracted 3×CH2Cl2 and dried over MgSO4, filtered, concentrated and purified by silica gel chromatography (100% EtOAc) to afford (2S,4R)-N-(4-Chloro-phenyl)-N-(2-methyl-1-{4-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-propoxy]-benzoyl}-1,2,3,4-tetrahydro-quinolin-4-yl)-acetamide in 44% yield.

Workup

  1. additionwas added
  2. temperatureheated
  3. temperatureto reflux for 4.5 h
  4. filtrationThe reaction was filtered
  5. concentrationconcentrated down
  6. custompartitioned between CH2Cl2 and water
  7. extractionThe aqueous layer was extracted 3×CH2Cl2
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified by silica gel chromatography (100% EtOAc)

Sources & evidence

ORD record
ord-01523886e92d415fa9c90295677c09d3
Source dataset
uspto-grants-2009_03
Patent number
US07504508B2

Reaction notes

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