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

HRID 2070317Notes

Reaction equation

HRID 2070317 reaction equation
[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

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-088a34b8e24d41d6bc1c1f6c068a38a1
Source dataset
uspto-grants-2012_10
Patent number
US08299108B2

Reaction notes

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