Potassium thiocyanate → (R)-N-benzyl-N-(2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethyl)-2-nitrobenzenesulfonamide

HRID 526725Notes

Reaction equation

HRID 526725 reaction equation
O[C@H]([C@@H](O)C(O)=O)C(O)=O.[F:11][C:12]1[CH:13]=[C:14]2[C:19](=[C:20]([F:22])[CH:21]=1)[O:18][CH2:17][C@H:16]([NH2:23])[CH2:15]2.[CH2:24]([N:31]([CH2:44][CH2:45][C:46](=O)[CH2:47]O)[S:32]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N+:41]([O-:43])=[O:42])(=[O:34])=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[S-:50][C:51]#[N:52].[K+].C(=O)(O)[O-].[Na+]>C(O)(=O)C.CC(O)C.O.C(O)C>[CH2:24]([N:31]([CH2:44][CH2:45][C:46]1[N:23]([C@@H:16]2[CH2:15][C:14]3[C:19](=[C:20]([F:22])[CH:21]=[C:12]([F:11])[CH:13]=3)[O:18][CH2:17]2)[C:51](=[S:50])[NH:52][CH:47]=1)[S:32]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[N+:41]([O-:43])=[O:42])(=[O:34])=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

9

Reactant 4

HCID 516872Potassium thiocyanateHCID 516892Sodium BicarbonateHCID 25118723(R)-6,8-difluorochroman-3-amine (2R,3R)-2,3-dihydroxysuccinateHCID 71152063N-benzyl-2-nitro-N-(4-hydroxy-3-oxobutyl)benzenesulfonamide2×

Product 1

HCID 71152068(R)-N-benzyl-N-(2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)ethyl)-2-nitrobenzenesulfonamideYield 64%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (R)-6,8-difluorochroman-3-amine(2R,3R)-2,3-dihydroxysuccinate (compound JT′, 1.7 g, 5.07 mmol), N-benzyl-N-(4-hydroxy-3-oxobutyl)-2-nitrobenzenesulfonamide (compound I, 2.303 g, 6.08 mmol) in acetic acid (12.5 ml) was added potassium thiocyanate (0.591 g, 6.08 mmol) in one portion. The mixture was heated with stirring at 100° C. for 3 hours under HPLC control, cooled to 20° C., diluted with 2-propanol (55 ml), cooled to 0° C., aged for 1 hour. The precipitate collected, washed with cold 2-propanol (55 ml), dried to give 12.54 g. The solid was suspended in a mixture of water (38 ml) and ethanol (EtOH) (19 ml), solid sodium bicarbonate (2.255 g, 26.8 mmol) was added in portions with stirring at 20-25° C., stirred for 30 min. Solid collected, washed with water, dried to give (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′, 8.4 g, 14.32 mmol, 64.0% yield).

Workup

  1. temperatureThe mixture was heated
  2. temperaturecooled to 20° C.
  3. temperaturecooled to 0° C.
  4. waitaged for 1 hour
  5. customThe precipitate collected
  6. washwashed with cold 2-propanol (55 ml)
  7. customdried
  8. customto give 12.54 g
  9. additionwas added in portions
  10. stirringwith stirring at 20-25° C.
  11. stirringstirred for 30 min
  12. customSolid collected
  13. washwashed with water
  14. customdried

Sources & evidence

ORD record
ord-ec3999171d0f43b2a28f78f2420ddff4
Source dataset
uspto-grants-2016_05
Patent number
US09346751B2

Reaction notes

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