1-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one → N-(5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777964Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1777964
[CH3:1][O:2][CH:3]([O:23][CH3:24])[C:4]1[C:13]([CH2:14][N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][C:16]2=[O:22])=[CH:12][C:11]2[CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[N:5]=1.C1([O:31][C:32](=O)[NH:33][C:34]2[CH:39]=[C:38]([O:40][CH2:41][CH2:42][O:43][CH3:44])[C:37]([C:45]#[N:46])=[CH:36][N:35]=2)C=CC=CC=1>CN(C1C=CN=CC=1)C.CC(N(C)C)=O>[C:45]([C:37]1[C:38]([O:40][CH2:41][CH2:42][O:43][CH3:44])=[CH:39][C:34]([NH:33][C:32]([N:7]2[C:6]3[C:11](=[CH:12][C:13]([CH2:14][N:15]4[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][C:16]4=[O:22])=[C:4]([CH:3]([O:23][CH3:24])[O:2][CH3:1])[N:5]=3)[CH2:10][CH2:9][CH2:8]2)=[O:31])=[N:35][CH:36]=1)#[N:46]

Komponenten

5

Edukt 2

HCID 1180366581-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one2×HCID 125470569Phenyl (5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)carbamate2×

Produkt 1

HCID 118037496N-(5-cyano-4-(2-methoxyethoxy)pyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one (intermediate 81, 1.03 g, 3.08 mmol), phenyl(5-cyano-4-(2-methoxyethoxyl)pyridin-2-yl)carbamate (intermediate 108, 2.19 g, 6.16 mmol) and DMAP (753 mg, 6.16 mmol) in DMA (15 ml) was heated at 90° C. for 3.5 h. The cooled reaction mixture was partitioned between EtOAc and, the organic layer dried over MgSO4 and evaporated. The residue was purified by reversed phase chromatography (RP 4) and the product containing fractions were partitioned between saturated aqueous NaHCO3 and EtOAc, the organic layer dried over MgSO4 and vaporated. The residue was then triturated with a mixture of DCM, Et2O and heptane to give the title compound as a white solid. (UPLC-MS 7) tR 0.80; ESI-MS 554.4 [M+H]+.

Aufarbeitung

  1. customThe cooled reaction mixture
  2. customwas partitioned between EtOAc
  3. dry with materialthe organic layer dried over MgSO4
  4. customevaporated
  5. customThe residue was purified by reversed phase chromatography (RP 4)
  6. additionthe product containing fractions
  7. customwere partitioned between saturated aqueous NaHCO3 and EtOAc
  8. dry with materialthe organic layer dried over MgSO4
  9. customThe residue was then triturated with a mixture of DCM, Et2O and heptane

Quellen und Nachweise

ORD-Eintrag
ord-81ac7cf972894f90a81c4c4cc7da1838
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266883B2

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