Benzaldehyde → 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 538940Notes

Reaction equation

HRID 538940 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[N:8]([C@@H:9]2[CH2:18][C:17]3[C:12](=[C:13]([F:20])[CH:14]=[C:15]([F:19])[CH:16]=3)[O:11][CH2:10]2)[C:7](=[S:21])[NH:6][CH:5]=1.[CH:22](=O)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([BH3-])#N.[Na+]>CO.ClCCl>[CH2:22]([NH:1][CH2:2][CH2:3][C:4]1[N:8]([C@@H:9]2[CH2:18][C:17]3[C:12](=[C:13]([F:20])[CH:14]=[C:15]([F:19])[CH:16]=3)[O:11][CH2:10]2)[C:7](=[S:21])[NH:6][CH:5]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 3

HCID 240BenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 10450387Etamicastat

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 50.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
22.5 °C

Procedure

To (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (2.36 g, 7.58 mmol) in a mixture of Methanol (15.00 ml) and Dichloromethane (15 ml) was added BENZALDEHYDE (0.845 ml, 8.34 mmol). To the resulting clear solution SODIUM CYANOBOROHYDRIDE (0.702 g, 10.61 mmol) was added in portions at 20-25° C. to avoid intensive foaming and the solution was stirred at 20-25° C. for 40 h. The solution was quenched at 20-25° C. with 1N HCl (12 ml), neutralised with 3N NaOH (12 ml), the mixture was extracted with DCM (100 ml). The organic phase was washed with brine, dried (MgSO4), evaporated to dryness. The residue was purified on a column with EA-MeOH 9:1 as eluent, fractions collected, concentrated to approx 20 ml, cooled in ice. The precipitate collected, washed with Ethyl Acetate-Petroleum Ether 1:1, dried on air to give (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (1.55 g, 3.86 mmol, 50.9% yield).

Workup

  1. customThe solution was quenched at 20-25° C. with 1N HCl (12 ml)
  2. extractionthe mixture was extracted with DCM (100 ml)
  3. washThe organic phase was washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated to dryness
  6. customThe residue was purified on a column with EA-MeOH 9:1 as eluent
  7. customfractions collected
  8. concentrationconcentrated to approx 20 ml
  9. temperaturecooled in ice
  10. customThe precipitate collected
  11. washwashed with Ethyl Acetate-Petroleum Ether 1:1
  12. customdried on air

Sources & evidence

ORD record
ord-ebfcc48699514d1fb5d359972f69bf96
Source dataset
uspto-grants-2014_10
Patent number
US08865913B2

Reaction notes

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