Sodium hydride → HCID 18506868, compound

HRID 1355479Notes

Reaction equation

HRID 1355479 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([CH:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19](=O)OC(C)(C)C)[CH:13]=2)[CH3:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[H-].[Na+].ClC1[S:30][C:31]([C:34]#[N:35])=[CH:32][N:33]=1>Cl.O1CCOCC1.O.C([O-])(O)=O.[Na+]>[C:1]([N:4]1[CH2:5][CH2:6][N:7]([CH:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[S:30][C:31]([C:34]#[N:35])=[CH:32][N:33]=3)[CH:13]=2)[CH3:11])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 14852222-Chlorothiazole-5-carbonitrileHCID 18506846HCID 18506846, compound

Product 1

HCID 18506868HCID 18506868, compound

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

tert-Butyl 4-[1-(4-acetylpiperazin-1-yl)ethyl]pyridin-2-ylcarbamate (16-4, 137 mg, 0.39 mmole) was taken up in 4 M HCl in dioxane (10 mL) at RT. After 60 hr the mixture was diluted with H2O and neutralized with solid NaHCO3. The resulting mixture was extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was taken up in dry THF (2 mL). To this was added NaH (40 mg, 60% dispersion in mineral oil, 0.98 mmole). After gas evolution had ceased 2-chloro-5-cyano-1,3-thiazole (85 mg, 0.59 mmole) was added and the mixture heated to reflux. After 3 hr the mixture was cooled to RT and quenched with saturated NH4Cl. The layers were separated and the aqueous layer extracted with EtOAc (4×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (gradient, 0-15% EtOH/EtOAc) gave the titled compound as a tan solid. 1H-NMR (500 MHz, d6-DMSO) δ12.18 (s, 1H), 8.34 (d, 1H, J=5.13 Hz), 8.26 (s, 1H), 7.12 (s, 1H), 7.05 (d, 1H, J=5.13 Hz), 3.52-3.41 (m, 5H), 2.44-2.03 (m, 4H), 1.96 (m, 3H), 1.28 (d, 3H, J=6.59 Hz); MS (ES) (M+H)+357.

Workup

  1. extractionThe resulting mixture was extracted with CH2Cl2 (3×)
  2. dry with materialThe combined organic layers were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. additionwas added
  6. temperaturethe mixture heated to reflux
  7. customquenched with saturated NH4Cl
  8. customThe layers were separated
  9. extractionthe aqueous layer extracted with EtOAc (4×)
  10. dry with materialThe combined organic layers were dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-80f273c4410e4b268f238b8bc3aa5413
Source dataset
uspto-grants-2003_07
Patent number
US06586423B2

Reaction notes

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