Hydrochloric Acid → [1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]1H-imidazol-2-yl]cyanamide

HRID 352428Notes

Reaction equation

HRID 352428 reaction equation
[C:1]([N:3]=[C:4]([NH:23][CH2:24][CH:25](OC)OC)[NH:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH:13]2[CH2:18][CH2:17][C:16]3[CH:19]=[CH:20][CH:21]=[CH:22][C:15]=3[O:14]2)[CH2:8][CH2:7]1)#[N:2].Cl.C([O-])([O-])=[O:32].[Na+].[Na+]>C1COCC1>[O:14]1[C:15]2[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=2[CH2:17][CH2:18][CH:13]1[CH2:12][N:9]1[CH2:10][CH2:11][CH:6]([N:5]2[CH:25]=[CH:24][N:23]=[C:4]2[NH:3][C:1]#[N:2])[CH2:7][CH2:8]1.[O:14]1[C:15]2[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=2[CH2:17][CH2:18][CH:13]1[CH2:12][N:9]1[CH2:8][CH2:7][CH:6]([N:5]2[CH:25]=[CH:24][N:23]=[C:4]2[NH:3][C:1]([NH2:2])=[O:32])[CH2:11][CH2:10]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 178495968HCID 178495968, compound

Product 2

HCID 9797906[1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]1H-imidazol-2-yl]cyanamideHCID 9841580(+/-)-[1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-1H-imidazol-2-yl]urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N″-cyano-N-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-N′-(2.2-dimethoxyethyl)guanidine (0.0153 mol) and HCl (0.5 N, 46 ml) in THF (160 ml) was stirred and refluxed for 100 minutes. Ice-water was added. Na2CO3 was added portionwise to obtain a clear separation. The organic layer was separated, DCM was added, the whole was washed with water, dried, filtered and the solvent was evaporated. The residue was separated and purified by column chromatography over silica gel (separation first compound: eluent: CH2Cl2/CH3OH 95/5; separation second compound: CH2Cl2/(CH3OH/NH3) 90/10). The two pure fraction groups were collected and their solvent was evaporated. Each residue was crystallized from ACN. Each precipitate was filtered off and dried, yielding 1.75 g [1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]1H-imidazol-2-yl]cyanamide (compound 59) and 0.48 g (±)-[1-[1-[(3,4-dihydro-2H-1-benzopyran-2-yl)methyl]-4-piperidinyl]-1H-imidazol-2-yl]urea (compound 66).

Workup

  1. temperaturerefluxed for 100 minutes
  2. customto obtain
  3. customa clear separation
  4. customThe organic layer was separated
  5. additionDCM was added
  6. washthe whole was washed with water
  7. customdried
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. customThe residue was separated
  11. custompurified by column chromatography over silica gel (separation first compound: eluent: CH2Cl2/CH3OH 95/5; separation second compound: CH2Cl2/(CH3OH/NH3) 90/10)
  12. customThe two pure fraction groups were collected
  13. customtheir solvent was evaporated
  14. customEach residue was crystallized from ACN
  15. filtrationEach precipitate was filtered off
  16. customdried

Sources & evidence

ORD record
ord-8be02292825c4477a2969b748dd3a61c
Source dataset
uspto-grants-2004_06
Patent number
US06747045B2

Reaction notes

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