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

HRID 340328

반응식

HRID 340328 반응식
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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 22253497Water butanol용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-05f00637c98c40b9b8ec9acf4acd25ee
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08895577B2

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