Sodium Hydroxide → 1-((3R)-6,8-Difluoro-3,4-dihydro-2H-1-benzopyran-3-yl)-1,3-dihydro-5-(2-((phenylmethyl)amino)ethyl)-2H-imidazole-2-thione

HRID 526729Notes

Reaction equation

HRID 526729 reaction equation
Cl.[CH2:2]([NH:9][CH2:10][CH2:11][C:12]1[N:16]([C@@H:17]2[CH2:26][C:25]3[C:20](=[C:21]([F:28])[CH:22]=[C:23]([F:27])[CH:24]=3)[O:19][CH2:18]2)[C:15](=[S:29])[NH:14][CH:13]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+]>CO.O>[CH2:2]([NH:9][CH2:10][CH2:11][C:12]1[N:16]([C@@H:17]2[CH2:26][C:25]3[C:20](=[C:21]([F:28])[CH:22]=[C:23]([F:27])[CH:24]=3)[O:19][CH2:18]2)[C:15](=[S:29])[NH:14][CH:13]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 25156755Zamicastat hydrochloride

Product 1

HCID 250526301-((3R)-6,8-Difluoro-3,4-dihydro-2H-1-benzopyran-3-yl)-1,3-dihydro-5-(2-((phenylmethyl)amino)ethyl)-2H-imidazole-2-thioneYield 91.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
67.5 °C

Procedure

(R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride (8 g, 18.27 mmol) was dissolved in methanol (120 ml) at 40-45° C., diluted with water (18.00 ml), crystallisation occurred. The precipitate was dissolved with heating to 67-68° C. and stirring. To the solution 1N sodium hydroxide (19.18 ml, 19.18 mmol) was added dropwise during 1 hour via a syringe pump. The mixture was aged for 30 min at 67° C., cooled to 20° C. during 1 hour, aged at 20° C. for 30 min. Crystals were collected, washed with MeOH-water 1:1 (36 ml), dried to give (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (6.7 g, 16.69 mmol, 91% yield).

Workup

  1. dissolutionThe precipitate was dissolved
  2. temperaturecooled to 20° C. during 1 hour
  3. waitaged at 20° C. for 30 min
  4. customCrystals were collected
  5. washwashed with MeOH-water 1:1 (36 ml)
  6. customdried

Sources & evidence

ORD record
ord-057cb92c22a44578841fff9dd5965822
Source dataset
uspto-grants-2016_05
Patent number
US09346751B2

Reaction notes

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