Hydrochloric Acid → HCID 86639134, compound

HRID 2189940Notes

Reaction equation

HRID 2189940 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[S:13][C:12]([CH2:20][CH2:21][C:22]#[N:23])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:11]([C:24](=[O:29])[C@@H:25]([O:27][CH3:28])[CH3:26])[N:10]=1.Cl.Cl.[O:32]([NH2:34])[CH3:33].C(N(CC)CC)C>C(O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[S:13][C:12]([CH2:20][CH2:21][C:22](=[N:34][O:32][CH3:33])[NH2:23])([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:11]([C:24](=[O:29])[C@@H:25]([O:27][CH3:28])[CH3:26])[N:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 68549380HCID 68549380, compound

Product 1

HCID 86639134HCID 86639134, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To cooled (0° C.) solution of 3-(5-(2,5-difluorophenyl)-3-((S)-2-methoxypropanoyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)propanenitrile (0.052 g, 0.13 mmol, Example 14, Step C) in ethanol (0.5 mL) was added 9.8 M ethanolic HCl (0.5 mL, 4.9 mmol). After stirring at room temperature for 6 hours, the mixture was concentrated under reduced pressure. To the residue was added methoxylamine hydrochloride (0.021 g, 0.21 mmol), absolute ethanol (0.5 mL) and triethylamine (0.087 mL, 0.63 mmol). After stirring at room temperature for 16 hours, the mixture was concentrated under reduced pressure. The residue was diluted with 10% Na2CO3 (30 mL) and extracted with dichloromethane. The combined organics were dried, filtered and concentrated under reduced pressure. The residue was chromatographed (40% ethyl acetate in hexanes) to afford the product as a mixture of diastereomers (14 mg, 25% yield). MS ESI (+) m/z 463 (M+1) detected; 1H NMR (4001 MHz, CDCl3) δ 7.50 (m, 2H), 7.38 (m, 8H), 7.30 (m, 2H), 7.13 (m, 4H), 4.78 (q, 1H, J=6.3 Hz), 4.72 (q, 1H, J=6.3 Hz), 4.64 (br. s, 4H), 3.77 (s, 6H), 3.54 (m, 2H), 3.41 (s, 3H), 3.36 (s, 3H), 2.68 (m, 4H), 2.18 (m, 2H), 1.51 (d, 3H, J=6.3 Hz), 1.49 (d, 3H, J=7.0 Hz).

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. stirringAfter stirring at room temperature for 16 hours
  3. concentrationthe mixture was concentrated under reduced pressure
  4. additionThe residue was diluted with 10% Na2CO3 (30 mL)
  5. extractionextracted with dichloromethane
  6. customThe combined organics were dried
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was chromatographed (40% ethyl acetate in hexanes)
  10. customto afford the product
  11. additionas a mixture of diastereomers (14 mg, 25% yield)

Sources & evidence

ORD record
ord-f9e9dcb15aca4012bec6dbe13e450922
Source dataset
uspto-grants-2012_12
Patent number
US08324257B2

Reaction notes

Loading…