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 599761Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 599761
[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

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 284Formic AcidKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-bbb0b1f890344a3895607c31b88e0f0f
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07897603B2

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