Triethylamine → Ethyl 1'-{(r)-3-(4-methyl-2-oxo-2,3-dihydro-benzoxazol-6-yl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1,4'-bipiperidinyl-4-carboxylate

HRID 1864626Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1864626
[O:1]=[C:2]1[N:8]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C@@H:18]([C:31](O)=[O:32])[CH2:19][C:20]3[CH:29]=[C:28]([CH3:30])[C:23]4[NH:24][C:25](=[O:27])[O:26][C:22]=4[CH:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH2:7][CH2:6][C:5]2[CH:34]=[CH:35][CH:36]=[CH:37][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.[N:67]1([CH:78]2[CH2:83][CH2:82][NH:81][CH2:80][CH2:79]2)[CH2:72][CH2:71][CH:70]([C:73]([O:75][CH2:76][CH3:77])=[O:74])[CH2:69][CH2:68]1>C1COCC1.CCOC(C)=O>[CH3:30][C:28]1[C:23]2[NH:24][C:25](=[O:27])[O:26][C:22]=2[CH:21]=[C:20]([CH2:19][C@@H:18]([O:17][C:15]([N:12]2[CH2:11][CH2:10][CH:9]([N:8]3[CH2:7][CH2:6][C:5]4[CH:34]=[CH:35][CH:36]=[CH:37][C:4]=4[NH:3][C:2]3=[O:1])[CH2:14][CH2:13]2)=[O:16])[C:31]([N:81]2[CH2:82][CH2:83][CH:78]([N:67]3[CH2:68][CH2:69][CH:70]([C:73]([O:75][CH2:76][CH3:77])=[O:74])[CH2:71][CH2:72]3)[CH2:79][CH2:80]2)=[O:32])[CH:29]=1

Komponenten

7

Edukt 4

HCID 8471Triethylamine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4778238[1,4']Bipiperidinyl-4-carboxylic acid ethyl esterHCID 68608307(R)-1-carboxy-2-(4-methyl-2-oxo-2,3-dihydrobenzoxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Produkt 1

HCID 16733968Ethyl 1'-{(r)-3-(4-methyl-2-oxo-2,3-dihydro-benzoxazol-6-yl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1,4'-bipiperidinyl-4-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 300 mg (0.59 mmol) (R)-1-carboxy-2-(4-methyl-2-oxo-2,3-dihydrobenz-oxazol-6-yl)-ethyl 4-(2-oxo-1,2,4,5,-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate, 210 mg (0.65 mmol) TBTU and 100 μL (0.72 mmol) triethylamine in 20 mL THF was stirred for 1 h at RT. Then 220 mg (0.70 mmol) ethyl [1,4′]bipiperidinyl-4-carboxylate (used as the bis-hydrochloride salt) and 400 μL (2.87 mmol) triethylamine were added. The reaction mixture was stirred for 24 h at RT. The mixture was diluted with EtOAc, the organic phase was washed with saturated NaHCO3 solution and dried on Na2SO4. After the desiccant and solvent had been eliminated the residue was purified by chromatography (Alox, activity grade II-III, gradient DCM/EtOH 20:1 to DCM/EtOH 10:1). The fractions containing the product were combined, evaporated down i. vac., the residue was triturated with diethyl ether, suction filtered and dried.

Aufarbeitung

  1. additionwere added
  2. washthe organic phase was washed with saturated NaHCO3 solution
  3. customdried on Na2SO4
  4. customwas purified by chromatography (Alox, activity grade II-III, gradient DCM/EtOH 20:1 to DCM/EtOH 10:1)
  5. additionThe fractions containing the product
  6. customevaporated down i
  7. custom, the residue was triturated with diethyl ether, suction
  8. filtrationfiltered
  9. customdried

Quellen und Nachweise

ORD-Eintrag
ord-0261f872fa7548c89bb4416d0831f165
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07625886B2

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