Lithium Hydroxide → Racemic 2-[5-Methyl-2-(3-piperidin-3-ylpropylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid cyclopropylamide

HRID 1986328Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1986328
[CH:1]1([NH:4][C:5]([C:7]2[C:15]3[CH:14]=[C:13]([C:16]4[C:21]([CH3:22])=[CH:20][N:19]=[C:18](Cl)[N:17]=4)[S:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1.C(OC([N:31]1[CH2:36][CH2:35][CH2:34][CH:33]([CH2:37][CH2:38][CH2:39][NH2:40])[CH2:32]1)=O)(C)(C)C.C(N(C(C)C)CC)(C)C.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O.[Li+].[OH-]>O1CCOCC1.ClCCl>[CH:1]1([NH:4][C:5]([C:7]2[C:15]3[CH:14]=[C:13]([C:16]4[C:21]([CH3:22])=[CH:20][N:19]=[C:18]([NH:40][CH2:39][CH2:38][CH2:37][CH:33]5[CH2:34][CH2:35][CH2:36][NH:31][CH2:32]5)[N:17]=4)[S:12][C:11]=3[CH:10]=[CH:9][CH:8]=2)=[O:6])[CH2:3][CH2:2]1

Komponenten

9

Edukt 6

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 81531DiisopropylethylamineHCID 68857542tert-Butyl 3-(3-aminopropyl)piperidine-1-carboxylateHCID 866253772-(2-Chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide

Produkt 1

HCID 68857359Racemic 2-[5-Methyl-2-(3-piperidin-3-ylpropylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid cyclopropylamideAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A stirred mixture of 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide (0.50 g, 1.5 mmol), racemic 3-(3-aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (0.88 g, 3.6 mmol) and diisopropylethylamine (0.47 g, 3.6 mmol) in 1,4-dioxane (7 mL) is heated at 90° C. under a nitrogen atmosphere for 48 hours. After concentration and subsequent chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 1-10%, the intermediate is obtained as a solid. The solid is suspended in dichloromethane (3 mL), followed by the successive addition of triethylsilane (0.50 mL) and TFA (3 mL), the resultant yellow solution is stirred for 16 hours. After concentration a wet solid is obtained. It is treated with 2 N LiOH, with sonication, until pH reaches 12. The mixture is filtered and the solid is dried before it is subjected to chromatography on silica gel, eluting with 2 M NH3/MeOH in dichloromethane 10-20%, to give the title compound as a yellow solid (160 mg, 25% yield). ES+(m/z) 450 [M+H].

Aufarbeitung

  1. concentrationAfter concentration and subsequent chromatography on silica gel
  2. washeluting with 2 M NH3/MeOH in dichloromethane 1-10%
  3. customthe intermediate is obtained as a solid
  4. concentrationAfter concentration a wet solid
  5. customis obtained
  6. filtrationThe mixture is filtered
  7. customthe solid is dried before it
  8. washeluting with 2 M NH3/MeOH in dichloromethane 10-20%

Quellen und Nachweise

ORD-Eintrag
ord-cc79490746f24f5b881d064a596ba0f1
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07547691B2

Notizen zur Reaktion

Wird geladen…