Hydrochloric Acid → Zamicastat hydrochloride

HRID 526728Notes

Reaction equation

HRID 526728 reaction equation
[CH2:1]([NH:8][CH2:9][CH2:10][C:11]1[N:15]([C@@H:16]2[CH2:25][C:24]3[C:19](=[C:20]([F:27])[CH:21]=[C:22]([F:26])[CH:23]=3)[O:18][CH2:17]2)[C:14](=[S:28])[NH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:29].C1(C)C=CC=CC=1>CO>[ClH:29].[CH2:1]([NH:8][CH2:9][CH2:10][C:11]1[N:15]([C@@H:16]2[CH2:25][C:24]3[C:19](=[C:20]([F:27])[CH:21]=[C:22]([F:26])[CH:23]=3)[O:18][CH2:17]2)[C:14](=[S:28])[NH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 250526301-((3R)-6,8-Difluoro-3,4-dihydro-2H-1-benzopyran-3-yl)-1,3-dihydro-5-(2-((phenylmethyl)amino)ethyl)-2H-imidazole-2-thione

Product 1

HCID 25156755Zamicastat hydrochlorideYield 94%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a suspension of (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (2 g, 4.98 mmol) in methanol (MeOH) (30 ml) was added 1.5M hydrochloric acid (3.32 ml, 4.98 mmol) in MeOH to give a clear solution. To the solution Toluene (30.0 ml) was added, MeOH (30 ml) was removed on a rotavap followed by addition of toluene (20 ml). The mixture was aged with stirring for 1 hours at 0-5° C., the precipitate collected, washed with toluene (10 ml), dried in vacuum at 50° C. to give 2.05 g (94%) of purified (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride.

Workup

  1. customto give a clear solution
  2. customMeOH (30 ml) was removed on a rotavap
  3. additionfollowed by addition of toluene (20 ml)
  4. customthe precipitate collected
  5. washwashed with toluene (10 ml)
  6. customdried in vacuum at 50° C.

Sources & evidence

ORD record
ord-2898f912a8ff4db5ba21eb52478c4128
Source dataset
uspto-grants-2016_05
Patent number
US09346751B2

Reaction notes

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