O-Phenylenediamine → {5-[2-(1H-Benzoimidazol-2-yl)-pyridin-4-yloxy]-1-methyl-1H-benzoimidazol-2-yl}-(4-fluoro-phenyl)-amine

HRID 1915694노트

반응식

HRID 1915694 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:13]([CH3:14])[C:12]3[CH:15]=[CH:16][C:17]([O:19][C:20]4[CH:25]=[CH:24][N:23]=[C:22]([C:26](O)=O)[CH:21]=4)=[CH:18][C:11]=3[N:10]=2)=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.[C:60]1([NH2:67])[CH:65]=[CH:64][CH:63]=[CH:62][C:61]=1[NH2:66].C([O-])(=O)C.[Na+]>C1COCC1.C(OCC)(=O)C>[NH:66]1[C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][C:60]=2[N:67]=[C:26]1[C:22]1[CH:21]=[C:20]([O:19][C:17]2[CH:16]=[CH:15][C:12]3[N:13]([CH3:14])[C:9]([NH:8][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[N:10][C:11]=3[CH:18]=2)[CH:25]=[CH:24][N:23]=1

참가 물질

9

반응물 6

HCID 7243O-PhenylenediamineHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 517045Sodium AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220412944-[2-(4-Fluoro-phenylamino)-1-methyl-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid

생성물 1

HCID 22040684{5-[2-(1H-Benzoimidazol-2-yl)-pyridin-4-yloxy]-1-methyl-1H-benzoimidazol-2-yl}-(4-fluoro-phenyl)-amine

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
70 °C

실험 절차

To a suspension of 4-[2-(4-Fluoro-phenylamino)-1-methyl-1H-benzoimidazol-5-yloxy]-pyridine-2-carboxylic acid (1 eq) in dry THF, EDC-HCl (1.2 eq), HOAT (1.2 eq), and diisopropylethylamine (3 eq) were added. The suspension was stirred for 10 minutes whereupon phenylenediamine (1.1 eq) was added and the solution is allowed to stir overnight. The mixture was then diluted with ethyl acetate and washed with water. The aqueous layer was washed with ethyl acetate, the organic layers combined, dried over MgSO4, filtered, and concentrated. Acetic acid was added to the residue followed by sodium acetate (1.1 eq). The mixture was heated for 3 hours at 70° C., whereupon the solution is concentrated and the residue purified by reverse phase HPLC to afford the desired product. LCMS m/z 451.5 (MH+), tR=1.92 min.

후처리

  1. additionwere added
  2. additionwas added
  3. washwashed with water
  4. washThe aqueous layer was washed with ethyl acetate
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additionAcetic acid was added to the residue
  9. concentrationis concentrated
  10. customthe residue purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-e076e140878c4c1a9f978476162410fa
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08614330B2

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