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Lithium hexamethyldisilazane → 6-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

HRID 1777932
ノート
印刷プレビュー

反応式

HRID 1777932 の反応式
[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:17](=[N:18][C:19]=1[CH:20]([O:23][CH3:24])[O:21][CH3:22])[N:16]([C:25](OC1C=CC=CC=1)=[O:26])[CH2:15][CH2:14][CH2:13]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[NH2:34][C:35]1[CH:42]=[C:41]([NH:43][CH2:44][CH2:45][O:46][CH3:47])[C:38]([C:39]#[N:40])=[CH:37][N:36]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]2[C:17](=[N:18][C:19]=1[CH:20]([O:21][CH3:22])[O:23][CH3:24])[N:16]([C:25]([NH:34][C:35]1[CH:42]=[C:41]([NH:43][CH2:44][CH2:45][O:46][CH3:47])[C:38]([C:39]#[N:40])=[CH:37][N:36]=1)=[O:26])[CH2:15][CH2:14][CH2:13]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 2733832Lithium hexamethyldisilazaneHCID 1180369516-Amino-4-((2-methoxyethyl)amino)nicotinonitrile2 回HCID 131734775phenyl 6-(((tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate2 回

生成物 1

HCID 1317347846-(((tert-butyldimethylsilyl)oxy)methyl)-N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-25 °C

実験手順

A solution of phenyl 6-(((tert-butyldimethylsilyl)oxy)methyl)-7-(dimethoxymethyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate (intermediate 38, 2.98 g, 6.29 mmol) and 6-amino-4-((2-methoxyethyl)amino)nicotinonitrile (intermediate 75, 1.10 g, 5.72 mmol) in THF (45 ml) at −70° C. (dry ice/2-PrOH bath, internal temperature) under argon was treated with LHMDS (1 M in THF, 12.6 ml, 12.6 mmol). The resulting solution was stirred with cooling for 35 min. The cooling bath was then removed and the reaction mixture was allowed to warm to −25° C., before being re-cooled to −70° C. The resulting solution was quenched with sat. aq. NH4Cl, allowed to warm to room temperature and extracted twice with EtOAc/heptanes 1:1. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (80 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100). The product containing fractions were concentrated and dried under vacuum to give the title compound as a white solid. (UPLC-MS 3) tR 1.60; ESI-MS 571.4 [M+H]+. 1H NMR (400 MHz, CDCl3-d) δ 13.81 (s, 1H), 8.23 (s, 1H), 7.74 (s, 1H), 7.57 (s, 1H), 5.45 (s, 1H), 5.26 (br s, 1H), 4.87 (s, 2H), 4.07-3.99 (m, 2H), 3.63 (t, 2H), 3.52-3.38 (m, 11H), 2.86 (t, 2H), 2.05-1.94 (m, 2H), 0.95 (s, 9H), 0.12 (s, 6H).

後処理

  1. temperaturewith cooling for 35 min
  2. customThe cooling bath was then removed
  3. temperaturebefore being re-cooled to −70° C
  4. customThe resulting solution was quenched with sat. aq. NH4Cl
  5. temperatureto warm to room temperature
  6. extractionextracted twice with EtOAc/heptanes 1:1
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude material was purified by normal phase chromatography (80 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100)
  12. additionThe product containing fractions
  13. concentrationwere concentrated
  14. customdried under vacuum

出典と根拠

ORDレコード
ord-4e62b2f019bc469aaf6614989077b6a8
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09266883B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート