Triethylamine → 4-(2-Oxo-1,4-dihydro-2h-quinazolin-3-yl)-piperidine-1-carboxylic acid[1-(6-benzyloxy-pyridin-3-ylmethyl)-2-[1,4']bipiperidinyl-1'-yl-2-oxo-ethyl]-amide

HRID 1177750Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1177750
CO[C:3](=[O:40])[CH:4]([NH:20][C:21]([N:23]1[CH2:28][CH2:27][CH:26]([N:29]2[CH2:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[NH:31][C:30]2=[O:39])[CH2:25][CH2:24]1)=[O:22])[CH2:5][C:6]1[CH:7]=[N:8][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH:11]=1.O.[OH-].[Li+].[N:44]1([CH:50]2[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]2)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1.C(N(CC)CC)C.[PH2](Cl)=O>CO.O>[CH2:13]([O:12][C:9]1[N:8]=[CH:7][C:6]([CH2:5][CH:4]([NH:20][C:21]([N:23]2[CH2:24][CH2:25][CH:26]([N:29]3[CH2:38][C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[NH:31][C:30]3=[O:39])[CH2:27][CH2:28]2)=[O:22])[C:3]([N:53]2[CH2:54][CH2:55][CH:50]([N:44]3[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]3)[CH2:51][CH2:52]2)=[O:40])=[CH:11][CH:10]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 786071,4'-BipiperidineHCID 168937Lithium hydroxide, monohydrateHCID 588642363-(6-benzyloxy-pyridin-3-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl esterHCID 178527016HCID 178527016, Verbindung

Produkt 1

HCID 100097694-(2-Oxo-1,4-dihydro-2h-quinazolin-3-yl)-piperidine-1-carboxylic acid[1-(6-benzyloxy-pyridin-3-ylmethyl)-2-[1,4']bipiperidinyl-1'-yl-2-oxo-ethyl]-amide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

To a stirred solution of 3-(6-benzyloxy-pyridin-3-yl)-2-{[4-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-piperidine-1-carbonyl]-amino}-propionic acid methyl ester (59 mg, 0.11 mmol) in methanol (3 mL) was added a solution of lithium hydroxide monohydrate (9.1 mg, 2 equiv) in water (0.5 mL). The reaction was stirred 2 h at room temperature, cooled to 0° C., quenched by addition of 1N hydrochloric acid (0.15 mL), and concentrated. The crude product was used without purification. The crude acid was dissolved in methylene chloride (2 mL, 0° C.), and treated sequentially with 4-piperidino-piperidine (34 mg, 1.8 equiv), triethylamine (35 μL, 2.3 equiv.), and bis-2-oxo-3-oxazolidinyl)phoshinic chloride (34 mg, 1.2 equiv). The ice bath was removed and the reaction allowed to stir overnight. The reaction was concentrated and purified by Prep TLC to give 30.3 mg (41%). LC/MS: tR=1.49 min, 680.29 (MH)+.

Aufarbeitung

  1. temperaturecooled to 0° C.
  2. customquenched by addition of 1N hydrochloric acid (0.15 mL)
  3. concentrationconcentrated
  4. customThe crude product was used without purification
  5. dissolutionThe crude acid was dissolved in methylene chloride (2 mL, 0° C.)
  6. customThe ice bath was removed
  7. stirringto stir overnight
  8. concentrationThe reaction was concentrated
  9. custompurified by Prep TLC
  10. customto give 30.3 mg (41%)

Quellen und Nachweise

ORD-Eintrag
ord-153aec0b4ea543cbb487849a1bc84556
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07842808B2

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