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

HRID 1777953ノート

反応式

HRID 1777953 の反応式
[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][CH:41]([CH3:43])[CH3:42])[C:37]([C:44]#[N:45])=[CH:36][N:35]=2)C=CC=CC=1>CN(C1C=CN=CC=1)C.C(#N)C>[C:44]([C:37]1[C:38]([O:40][CH:41]([CH3:43])[CH3:42])=[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:45]

参加物

5

反応物 2

HCID 1180366581-((2-(Dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one2 回HCID 125470513Phenyl (5-cyano-4-isopropoxypyridin-2-yl)carbamate2 回

生成物 1

HCID 118036852N-(5-cyano-4-isopropoxypyridin-2-yl)-7-(dimethoxymethyl)-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6342Acetonitrile溶媒

実験手順

A mixture of 1-((2-(dimethoxymethyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl)-4-methylpiperazin-2-one (intermediate 81, 268 mg, 0.641 mmol), phenyl(5-cyano-4-isopropoxypyridin-2-yl)carbamate (intermediate 96, 834 mg, 1.122 mmol) and DMAP (7.83 mg, 0.064 mmol) in acetonitrile (2.6 ml) was heated at reflux for 3.5 h. The reaction mixture was evaporated and applied to a 24 g RediSep silica column as a DCM solution and purified by normal phase chromatography, eluting with a gradient from DCM to 10% MeOH in DCM. Product containing fractions were combined and evaporated to give the title compound as an off-white solid. (UPLC-MS 6) tR 0.92; ESI-MS 538.7 [M+H]+.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 3.5 h
  3. customThe reaction mixture was evaporated
  4. custompurified by normal phase chromatography
  5. washeluting with a gradient from DCM to 10% MeOH in DCM
  6. additionProduct containing fractions
  7. customevaporated

出典と根拠

ORDレコード
ord-82f64929ec10405daba0be11b354598f
出典データセット
uspto-grants-2016_02
特許番号
US09266883B2

反応ノート

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