Triethylamine → (R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-oxo-2-{1'-[2-(2-oxo-pyrrolidin-1-yl)-ethoxycarbonyl-methyl]-4,4'-bipiperidinyl-1-yl}-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 730666Notes

Reaction equation

HRID 730666 reaction equation
[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@H:18]([CH2:37][C:38]3[CH:43]=[C:42]([CH3:44])[C:41]([OH:45])=[C:40]([CH3:46])[CH:39]=3)[C:19]([N:21]3[CH2:26][CH2:25][CH:24]([CH:27]4[CH2:32][CH2:31][N:30]([CH2:33][C:34]([OH:36])=[O:35])[CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:47]=[CH:48][CH:49]=[CH:50][C:4]=2[NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.O[CH2:81][CH2:82][N:83]1[CH2:87][CH2:86][CH2:85][C:84]1=[O:88]>CN(C=O)C.C(O)=O>[O:1]=[C:2]1[N:8]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C@H:18]([CH2:37][C:38]3[CH:43]=[C:42]([CH3:44])[C:41]([OH:45])=[C:40]([CH3:46])[CH:39]=3)[C:19](=[O:20])[N:21]3[CH2:22][CH2:23][CH:24]([CH:27]4[CH2:32][CH2:31][N:30]([CH2:33][C:34]([O:36][CH2:81][CH2:82][N:83]5[CH2:87][CH2:86][CH2:85][C:84]5=[O:88])=[O:35])[CH2:29][CH2:28]4)[CH2:25][CH2:26]3)=[O:16])[CH2:13][CH2:14]2)[CH2:7][CH2:6][C:5]2[CH:47]=[CH:48][CH:49]=[CH:50][C:4]=2[NH:3]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 769801-(2-Hydroxyethyl)-2-pyrrolidinoneHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 23654915(R)-2-(1'-carboxymethyl-4,4'-bipiperidinyl-1-yl)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 16123891(R)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-oxo-2-{1'-[2-(2-oxo-pyrrolidin-1-yl)-ethoxycarbonyl-methyl]-4,4'-bipiperidinyl-1-yl}-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 284Formic AcidCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 80 mg (0.12 mmol) (R)-2-(1′-carboxymethyl-4,4′-bipiperidinyl-1-yl)-1-(4-hydroxy-3,5-dimethyl-benzyl)-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate, 45 mg (0.14 mmol) TBTU and 32 μL (0.23 mmol) triethylamine in 1.2 mL DMF was stirred for 1 h at RT. Then 26 mg (0.23 mmol) 1-(2-hydroxy-ethyl)-pyrrolidin-2-one were added and the reaction mixture was stirred overnight at RT. The reaction solution was mixed with 5 drops of formic acid, filtered through a syringe filter and purified directly by HPLC without any further working up. The fractions containing the product were combined, extracted with 30 mL EtOAc, the organic phase was made alkaline with 5% NaHCO3 solution, separated off and dried on Na2SO4. After the elimination of the desiccant and solvent the residue was triturated with DIPE, suction filtered and dried.

Workup

  1. filtrationfiltered through a syringe
  2. filtrationfilter
  3. custompurified directly by HPLC without
  4. additionThe fractions containing the product
  5. extractionextracted with 30 mL EtOAc
  6. customseparated off
  7. customdried on Na2SO4
  8. customAfter the elimination of the desiccant and solvent the residue was triturated with DIPE, suction
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-57f991a4691e4d56ac62c7c516aae94e
Source dataset
uspto-grants-2009_09
Patent number
US07582625B2

Reaction notes

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