Triethylamine → N-(2-Amino-phenyl)-4-{2-[(pyridin-3-ylmethyl)-carbamoyl]-vinyl}-benzamide

HRID 1180803Notes

Reaction equation

HRID 1180803 reaction equation
N1(O[C:11]([CH:13]=[CH:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21]C)=O)=[CH:17][CH:16]=2)=[O:12])C2C=CC=CC=2N=N1.CCN(CC)CC.CN([P+](O[N:43]1N=[N:50][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][C:44]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[NH2:59][CH2:60][C:61]1[CH:62]=[N:63][CH:64]=[CH:65][CH:66]=1.[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[NH2:50][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=1[NH:43][C:19](=[O:21])[C:18]1[CH:17]=[CH:16][C:15]([CH:14]=[CH:13][C:11](=[O:12])[NH:59][CH2:60][C:61]2[CH:62]=[N:63][CH:64]=[CH:65][CH:66]=2)=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 8471Triethylamine2×HCID 25517Ammonium ChlorideHCID 310183-PyridinemethanamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 72479810Methyl 4-[2-(benzotriazol-1-yloxycarbonyl)-vinyl]-benzoate

Product 1

HCID 68976549N-(2-Amino-phenyl)-4-{2-[(pyridin-3-ylmethyl)-carbamoyl]-vinyl}-benzamideYield 92%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution at room temperature of VIII (140 mg, 0.68 mmol) in anhydrous DMF (5 ml) under nitrogen were added Et3N (104 μl, 0.75 mmol) and BOP reagent (331 mg, 0.75 mmol), respectively. After 30 min, a solution of 3-(aminomethyl)pyridine (90 μl, 0.88 mmol) or R1R2NH (1.2–1.3 equiv.), Et3N (284 μl, 2.04 mmol) in anhydrous DMF (2 ml) was added dropwise. After 4 h, the reaction mixture was poured into a saturated aqueous solution of NH4Cl, and diluted with AcOEt. After separation, the organic layer was successively washed with sat NH4Cl, H2O and brine, dried over MgSO4, filtered, and concentrated. The crude residue was then purified by flash chromatography on silica gel (MeOH/CH2Cl2:5/95→7/93) to afford the title compound IXb (185 mg, 0.62 mmol, 92% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ(ppm): 8.67–8.44 (m, 2H), AB system (δA=8.03, δB=7.55, J=8.4 Hz, 4H), 7.78–7.64 (m, 2H), 7.33–7.26 (m, 1H), 6.54 (d, J=15.8 Hz, 1H), 6.38 (bs, 1H), 4.61 (d, J=6.2 Hz, 2H), 3.92 (s, 3H).

Workup

  1. waitAfter 4 h
  2. customAfter separation
  3. washthe organic layer was successively washed with sat NH4Cl, H2O and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was then purified by flash chromatography on silica gel (MeOH/CH2Cl2:5/95→7/93)

Sources & evidence

ORD record
ord-4dabe5dcbd0248c1a4326d786e4d1009
Source dataset
uspto-grants-2007_10
Patent number
US07282608B2

Reaction notes

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