Sodium Carbonate → Methyl 5-amino-2-(4-methoxyphenethyl)benzo[f][1,7]naphthyridine-8-carboxylate

HRID 340311ノート

反応式

HRID 340311 の反応式
C(OC(NC1[CH:14]=[C:13]([C:15]([O:17][CH3:18])=[O:16])[CH:12]=CC=1B(O)O)=O)(C)(C)C.Cl[C:23]1N=[C:29]([CH2:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26].ClC1[C:43]([C:49]#[N:50])=[N:44][CH:45]=C(Cl)C=1.C(C1C=CC(OC)=CC=1)#C.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.O>[NH2:50][C:49]1[C:43]2[N:44]=[CH:45][C:29]([CH2:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)=[CH:28][C:27]=2[C:24]2[CH:23]=[CH:14][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:12][C:25]=2[N:26]=1

参加物

9

反応物 5

HCID 10340Sodium CarbonateHCID 2510201-Ethynyl-4-methoxybenzeneHCID 27696993,5-Dichloro-2-cyanopyridineHCID 668752372-(Tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenylboronic acidHCID 866523562-Chloro-6-(4-methoxyphenethyl)nicotinonitrile

生成物 1

HCID 58213534Methyl 5-amino-2-(4-methoxyphenethyl)benzo[f][1,7]naphthyridine-8-carboxylate

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 21863594Toluene ethanol溶媒

反応条件

温度
100 °C

実験手順

A solution of 2-(tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenylboronic acid (from Example 85/Step 1) (1.0 eq.) and 2-chloro-6-(4-methoxyphenethyl)nicotinonitrile (prepared from reaction of 3,5-dichloropicolinonitrile with 1-ethynyl-4-methoxybenzene following the procedure described in Example 44/Step 3 and reduction of the product following the procedure described in Example 114/Step 3) (1.0 eq.), tetrakis(triphenyl-phosphine)palladium (5 mol %), and 2N aqueous sodium carbonate solution (2.0 eq.) in toluene/ethanol (2:1, 0.03 M) was stirred at 100° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and water. The two phases were separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-80% EtOAc/Hexanes to give methyl 5-amino-2-(4-methoxyphenethyl)benzo[f][1,7]naphthyridine-8-carboxylate as a white solid.

後処理

  1. temperatureAfter cooling to ambient temperature
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated en vacuo
  7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

出典と根拠

ORDレコード
ord-4b2100ff81214bd5aec22fecc0c658df
出典データセット
uspto-grants-2014_11
特許番号
US08895577B2

反応ノート

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