Water → 4-{3-[4-(3-{4-[amino(butoxycarbonylimino)methyl]phenoxy}propyl)-1-piperidinyl]propoxy}-N'-(butoxycarbonyl)benzamidine

HRID 43282Notes

Reaction equation

HRID 43282 reaction equation
[C:1](=[O:17])([O:7][C:8]1[CH:13]=[CH:12][C:11]([N+]([O-])=O)=CC=1)OCCCC.[NH2:18][C:19](=[NH:49])[C:20]1[CH:48]=[CH:47][C:23]([O:24][CH2:25][CH2:26][CH2:27][CH:28]2[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][O:37][C:38]3[CH:46]=[CH:45][C:41]([C:42]([NH2:44])=[NH:43])=[CH:40][CH:39]=3)[CH2:30][CH2:29]2)=[CH:22][CH:21]=1.C(Cl)(Cl)Cl.[OH2:54]>CN(C)C=O>[NH2:49][C:19](=[N:18][C:1]([O:7][CH2:8][CH2:13][CH2:12][CH3:11])=[O:17])[C:20]1[CH:48]=[CH:47][C:23]([O:24][CH2:25][CH2:26][CH2:27][CH:28]2[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][O:37][C:38]3[CH:39]=[CH:40][C:41]([C:42]([NH2:44])=[N:43][C:1]([O:7][CH2:8][CH2:13][CH2:12][CH3:11])=[O:54])=[CH:45][CH:46]=3)[CH2:30][CH2:29]2)=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6212ChloroformHCID 9803135T-2307 free baseHCID 12867351Butyl 4-nitrophenyl carbonate

Product 1

HCID 669199654-{3-[4-(3-{4-[amino(butoxycarbonylimino)methyl]phenoxy}propyl)-1-piperidinyl]propoxy}-N'-(butoxycarbonyl)benzamidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a solution of 1.82 g of butyl 4-nitrophenyl carbonate in 15 mL of N,N-dimethylformamide, 1.50 g of 4-{3-[4-(3-{4-[amino(imino)methyl]phenoxy}propyl)-1-piperidinyl]propoxy}benzamidine was added at room temperature, and the solution was stirred at the same temperature for 2 hours. Chloroform and water were added to the reaction mixture. The organic layer was separated, washed twice with a 5% potassium carbonate aqueous solution and with a saturated sodium chloride aqueous solution successively, and dried over anhydrous magnesium sulfate, followed by solvent removal by evaporation under reduced pressure. The obtained residue was purified by a silica gel column chromatography (eluent; chloroform:methanol=4:1). The obtained solid substance was dissolved in chloroform, washed twice with a 5% potassium carbonate aqueous solution and with a saturated sodium chloride aqueous solution successively, and dried over anhydrous magnesium sulfate. After removing the solvent by evaporation under reduced pressure, 1.39 g of 4-{3-[4-(3-{4-[amino(butoxycarbonylimino)methyl]phenoxy}propyl)-1-piperidinyl]propoxy}-N′-(butoxycarbonyl)benzamidine was obtained as a white solid.

Workup

  1. customThe organic layer was separated
  2. washwashed twice with a 5% potassium carbonate aqueous solution and with a saturated sodium chloride aqueous solution successively
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customfollowed by solvent removal by evaporation under reduced pressure
  5. customThe obtained residue was purified by a silica gel column chromatography (eluent; chloroform:methanol=4:1)
  6. dissolutionThe obtained solid substance was dissolved in chloroform
  7. washwashed twice with a 5% potassium carbonate aqueous solution and with a saturated sodium chloride aqueous solution successively
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customAfter removing the solvent
  10. customby evaporation under reduced pressure

Sources & evidence

ORD record
ord-2188da8ec0a24083a7f4abc19e5e2214
Source dataset
uspto-grants-2013_09
Patent number
US08536343B2

Reaction notes

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