Potassium Phosphate, Tribasic → N-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)phenyl)acetamide

HRID 340328

反応式

HRID 340328 の反応式
Cl[C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:21])[CH3:20])=[CH:14][CH:13]=2)[CH:5]=[N:6][C:7]=1[C:8]#[N:9].C[C:23]1[CH:28]=[CH:27][C:26]([NH:29]C(=O)OC(C)(C)C)=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=1.[CH:46]1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)CCC.O.C(OCC)(=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:9][C:8]1[C:7]2[N:6]=[CH:5][C:4]([CH2:10][CH2:11][C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:21])[CH3:20])=[CH:14][CH:13]=3)=[CH:3][C:2]=2[C:27]2[CH:28]=[CH:23][C:24]([CH3:46])=[CH:25][C:26]=2[N:29]=1

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 66875763N-(4-(2-(5-chloro-6-cyanopyridin-3-yl)ethyl)phenyl)acetamideHCID 66893267Tert-butyl 4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate

生成物 1

HCID 44231533N-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)phenyl)acetamide

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 22253497Water butanol溶媒

実験手順

A solution of N-(4-(2-(5-chloro-6-cyanopyridin-3-yl)ethyl)phenyl)acetamide (from the previous step) (1.0 eq.), tert-butyl 4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from Example 5/Step 2) (1.5 eq.), Tris(dibenzylideneacetone)dipalladium(0) (10 mol %), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (20 mol %), and potassium phosphate (2.0 eq.) in n-butanol /H2O (2.5:1, 0.04 M) was stirred at 100° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate and water. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. 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% ethyl acetate in hexane to give N-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)phenyl)acetamide as a white solid. 1H NMR (CDCl3): δ 8.51 (s, 1H), 8.32 (s, 1H), 8.01 (d, 1H), 7.44 (s, 1H), 7.33-7.36 (m, 2H), 7.03-7.19 (m, 3H), 5.98 (br, 2H), 3.07-3.11 (m, 2H), 2.94-2.98 (m, 2H), 2.44 (s, 3H), 2.10 (s, 3H). LRMS [M+H]=371.2.

後処理

  1. customwas stirred at 100° C. overnight
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with ethyl acetate
  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-05f00637c98c40b9b8ec9acf4acd25ee
出典データセット
uspto-grants-2014_11
特許番号
US08895577B2

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