Hydrochloric Acid → HCID 178501949, compound

HRID 2401829Notes

Reaction equation

HRID 2401829 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:38])[C:9]2[C:10]([C:36]#[N:37])=[C:11]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:35])[O:33][CH3:34])[CH:26]=3)[S:12][C:13]=2[C:14]2[N:18]=[CH:17][N:16](C3CCCCO3)[N:15]=2)=[CH:4][CH:3]=1.O1CCOCC1.Cl.O>CCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([OH:38])[C:9]2[C:10]([C:36]#[N:37])=[C:11]([C:25]3[CH:30]=[CH:29][N:28]=[C:27]([NH:31][C:32](=[O:35])[O:33][CH3:34])[CH:26]=3)[S:12][C:13]=2[C:14]2[NH:18][CH:17]=[N:16][N:15]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 312751,4-DioxaneHCID 68100372Methyl (4-{4-[(4-chlorophenyl)(hydroxy)methyl]-3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate

Product 1

HCID 178501949HCID 178501949, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To a suspension of methyl (4-{4-[(4-chlorophenyl)(hydroxy)methyl]-3-cyano-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-2-thienyl}pyridin-2-yl)carbamate (0.0450 g, 0.0817 mmol) in 1,4-dioxane (4.0 mL, 51 mmol) and cooled in an ice bath was added 6.0 M hydrochloric acid in water (4.0 mL, 24 mmol). The resulting solution was brought to room temperature. Hexane (5.0 mL) was added and the bi layer mixture was stirred for 4 hours. The hexane was separated and the aqueous layer was washed with hexane twice. The aqueous layer was concentrated on a rotavapor to ˜half volume, diluted with ice and water, basified with saturated aqueous NaHCO3 to pH ˜7.5, extracted with EtOAc (4×). The combined EtOAc solutions were washed with brine, dried over Na2SO4, filtered, and rotavaped to give a crude solid. The crude solid was chromatographed on a silica gel column using MeOH/DCM (0/100 to 5/95) to afford a solid product (33 mg, yield 82%). LC/MS: (FA) ES+ 467, 469. 1H NMR (400 MHz, d6-dmso) δ 10.50 (s, 1H), 8.82 (s, 1H), 8.41 (m, 1H), 8.20 (s, 1H), 7.57 (m, 2H), 7.39 (m, 3H), 7.06 (s, 1H), 6.59 (s, br, 1H), 3.69 (s, 3H).

Workup

  1. temperaturecooled in an ice bath
  2. customwas brought to room temperature
  3. customThe hexane was separated
  4. washthe aqueous layer was washed with hexane twice
  5. concentrationThe aqueous layer was concentrated on a rotavapor to ˜half volume
  6. additiondiluted with ice and water
  7. extractionextracted with EtOAc (4×)
  8. washThe combined EtOAc solutions were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customto give a crude solid
  12. customThe crude solid was chromatographed on a silica gel column

Sources & evidence

ORD record
ord-d90939e7486945bbb18860a94b450274
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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