Hydrochloric Acid → Nepicastat hydrochloride anhydrous

HRID 863083Notes

Reaction equation

HRID 863083 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([F:12])[CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][C@H:6]([N:13]1[C:17]([CH2:18][NH:19]C=O)=[CH:16][NH:15][C:14]1=[S:22])[CH2:7]2.[ClH:23].CS(C)=O>C(O)(C)C>[ClH:23].[NH2:19][CH2:18][C:17]1[N:13]([C@H:6]2[CH2:5][CH2:4][C:3]3[C:8](=[CH:9][C:10]([F:12])=[CH:11][C:2]=3[F:1])[CH2:7]2)[C:14](=[S:22])[NH:15][CH:16]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 15290001HCID 15290001, compound

Product 1

HCID 9840545Nepicastat hydrochloride anhydrousYield 79.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of (S)-N-[3-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-ylmethyl]formamide (19.1 g, 59.0 mmol), prepared as in Example 30, and 25 mL of concentrated hydrochloric acid (12.0M, 25 mL, 300 mmol) in 400 mL of isopropanol was heated to reflux over 12 minutes and stirred for 1 hour 40 minutes. The mixture was distilled removing 150 mL of isopropanol. The mixture was gradually cooled to room temperature and stirred for 3 hours 45 minutes. The material was isolated by filtration and the filter residue was washed with 75 mL of isopropanol. Drying in vacuo at 110° to 125° C. with a nitrogen bleed gave (S)-5-aminomethyl-1-(5,7-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)-1,3-dihydroimidazole-2-thione hydrochloride (15.6 g, 47.1 mmol), m.p. 251.9° C. [α]D +10.2° C. (c=0.500, DMSO).

Workup

  1. temperaturewas heated
  2. temperatureto reflux over 12 minutes
  3. distillationThe mixture was distilled
  4. customremoving 150 mL of isopropanol
  5. stirringstirred for 3 hours 45 minutes
  6. customThe material was isolated by filtration
  7. washthe filter residue was washed with 75 mL of isopropanol
  8. customDrying in vacuo at 110° to 125° C. with a nitrogen bleed

Sources & evidence

ORD record
ord-b586fc608c5c44829a0369771bc144a8
Source dataset
uspto-grants-1998_02
Patent number
US05719280

Reaction notes

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