Ethyl 4-piperidinecarboxylate → Ethyl 1-{isopropyl[3-({3-[(4-{3-[4-(methoxycarbonyl)phenyl]propyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)benzyl]carbamoyl}piperidine-4-carboxylate

HRID 2176017Notes

Reaction equation

HRID 2176017 reaction equation
[CH:1]([NH:4][CH2:5][C:6]1[CH:7]=[C:8]([CH:43]=[CH:44][CH:45]=1)[C:9]([NH:11][C:12]1[S:13][C:14]2[CH2:42][CH2:41][CH2:40][CH2:39][C:15]=2[C:16]=1[C:17]([NH:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH2:28][C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=2)=[CH:22][CH:21]=1)=[O:18])=[O:10])([CH3:3])[CH3:2].Cl[C:47](Cl)([O:49]C(=O)OC(Cl)(Cl)Cl)Cl.[NH:58]1[CH2:68][CH2:67][CH:61]([C:62]([O:64][CH2:65][CH3:66])=[O:63])[CH2:60][CH2:59]1.C(=O)([O-])O.[Na+]>C(N(CC)CC)C.C1COCC1>[CH:1]([N:4]([CH2:5][C:6]1[CH:45]=[CH:44][CH:43]=[C:8]([C:9](=[O:10])[NH:11][C:12]2[S:13][C:14]3[CH2:42][CH2:41][CH2:40][CH2:39][C:15]=3[C:16]=2[C:17](=[O:18])[NH:19][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH2:28][C:29]3[CH:30]=[CH:31][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:37][CH:38]=3)=[CH:22][CH:21]=2)[CH:7]=1)[C:47]([N:58]1[CH2:59][CH2:60][CH:61]([C:62]([O:64][CH2:65][CH3:66])=[O:63])[CH2:67][CH2:68]1)=[O:49])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 70770Ethyl 4-piperidinecarboxylateHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 90370278Methyl 4-{3-[4-({[2-({3-[(isopropylamino)methyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]propyl}benzoate

Product 1

HCID 90370183Ethyl 1-{isopropyl[3-({3-[(4-{3-[4-(methoxycarbonyl)phenyl]propyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)benzyl]carbamoyl}piperidine-4-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 150 mg of methyl 4-{3-[4-({[2-({3-[(isopropylamino)methyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]propyl}benzoate and 3.5 mL of THF was added 0.045 mL of triethylamine and 28 mg of triphosgene under ice cooling, followed by stirring for 3 hours at room temperature. Thereafter, 0.080 mL of ethyl isonipecotate was added to the reaction mixture, followed by stirring for 18 hours at room temperature. An aqueous sodium hydrogen carbonate solution was added to the reaction mixture, followed by stirring for 1 hour at room temperature, and then extraction was performed using chloroform. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was purified by basic silica gel column chromatography (NH silica gel manufactured by FUJI SILYSIA CHEMICAL LTD. (amino type silica gel (treated with aminopropyl)), (hexane:ethyl acetate=1:1)), thereby obtaining 178 mg of ethyl 1-{isopropyl[3-({3-[(4-{3-[4-(methoxycarbonyl)phenyl]propyl}phenyl)carbamoyl]-4,5,6,7-tetrahydro-1-benzothiophen-2-yl}carbamoyl)benzyl]carbamoyl}piperidine-4-carboxylate.

Workup

  1. stirringby stirring for 18 hours at room temperature
  2. stirringby stirring for 1 hour at room temperature
  3. extractionextraction
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was purified by basic silica gel column chromatography (NH silica gel manufactured by FUJI SILYSIA CHEMICAL LTD. (amino type silica gel (treated with aminopropyl)), (hexane:ethyl acetate=1:1))

Sources & evidence

ORD record
ord-b50b2a18cadf4f548bcc485375c629fd
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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