Water → 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 526726Notes

Reaction equation

HRID 526726 reaction equation
[CH2:1]([N:8]([CH2:21][CH2:22][C:23]1[N:24]([C@@H:29]2[CH2:38][C:37]3[C:32](=[C:33]([F:40])[CH:34]=[C:35]([F:39])[CH:36]=3)[O:31][CH2:30]2)[C:25](=[S:28])[NH:26][CH:27]=1)S(C1C=CC=CC=1[N+]([O-])=O)(=O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.SCC(O)=O.[OH-].[K+].O>CN(C)C=O.CO.O>[CH2:1]([NH:8][CH2:21][CH2:22][C:23]1[N:24]([C@@H:29]2[CH2:38][C:37]3[C:32](=[C:33]([F:40])[CH:34]=[C:35]([F:39])[CH:36]=3)[O:31][CH2:30]2)[C:25](=[S:28])[NH:26][CH:27]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 1133Thioglycolic AcidHCID 14797Potassium HydroxideHCID 71152068(R)-N-benzyl-N-(2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethyl)-2-nitrobenzenesulfonamide

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%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
22.5 °C

Procedure

To a solution of (R)—N-benzyl-N-(2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethyl)-2-nitrobenzenesulfonamide (compound K′, 8 g, 13.64 mmol) and 2-mercaptoacetic acid (2.84 ml, 40.9 mmol) in dimethylformamide (DMF) (80 ml) was added 10N potassium hydroxide (10.23 ml, 102 mmol) in one portion with water cooling and the mixture was stirred at 20-25° C. under HPLC control for 3 hours. Methanol-water 1:1 (160 ml) was slowly added with stirring, the mixture was stirred for 2 hours at 20-25° C. Precipitate was collected, washed with MeOH-water 1:1 (80 ml), dried to give (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (4.96 g, 12.35 mmol, 91% yield).

Workup

  1. stirringwith stirring
  2. stirringthe mixture was stirred for 2 hours at 20-25° C
  3. customPrecipitate was collected
  4. washwashed with MeOH-water 1:1 (80 ml)
  5. customdried

Sources & evidence

ORD record
ord-6d5404eec536408196cb9e5a97d7dc55
Source dataset
uspto-grants-2016_05
Patent number
US09346751B2

Reaction notes

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