3-Chloroaniline → N-(3-chlorophenyl)-4-(3-ethylureido)-2-(phenylamino)benzamide

HRID 2174229Notes

Reaction equation

HRID 2174229 reaction equation
Cl.[CH2:2](N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[CH2:24]([NH:26][C:27](=[O:45])[NH:28][C:29]1[CH:37]=[C:36]([NH:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:32]([C:33]([OH:35])=O)=[CH:31]N=1)[CH3:25].C(NC(=O)NC1C=C(NCC2C=NC=CC=2)C(C(O)=O)=CN=1)C.[Cl:69][C:70]1[CH:71]=[C:72]([CH:74]=[CH:75][CH:76]=1)[NH2:73]>CN(C=O)C>[Cl:69][C:70]1[CH:71]=[C:72]([NH:73][C:33](=[O:35])[C:32]2[CH:31]=[CH:2][C:29]([NH:28][C:27]([NH:26][CH2:24][CH3:25])=[O:45])=[CH:37][C:36]=2[NH:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:74]=[CH:75][CH:76]=1

Participants

7

Reactant 5

HCID 79323-ChloroanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 896500056-(3-Ethylureido)-4-(phenylamino)nicotinic acidHCID 896505966-(3-Ethylureido)-4-(pyridin-3-ylmethylamino)nicotinic acid

Product 1

HCID 89650711N-(3-chlorophenyl)-4-(3-ethylureido)-2-(phenylamino)benzamideYield 16%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.092 g, 0.480 mmol) and 1-hydroxybenzotriazole monohydrate (0.073 g, 0.480 mmol) were added to a stirred solution of 6-(3-ethylureido)-4-(phenylamino)nicotinic acid, vi (0.100 g, 0.320 mmol) in DMF (3 mL) at room temperature. After 15 min, 3-chloroaniline (0.061 g, 0.480 mmol) was added and the reaction mixture stirred at 40° C. for 24 h. The mixture was cooled to room temperature, poured onto water and extracted with EtOAc (3×30 mL). The combined organic phase was washed successively with water (20 mL), saturated aqueous sodium bicarbonate (20 mL) and brine (2×20 mL), dried (MgSO4), and reduced in vacuo to give the crude product. This was triturated with EtOAc to afford Compound 4 (0.021 g, 0.051 mmol, 16%) as a colourless powder. 1H NMR (300 MHz, DMSO-d6): δ 10.44 (1H, s), 9.83 (1H, s), 9.16 (1H, s), 8.58 (1H, s), 7.96-7.90 (2H, m), 7.63 (1H, d, J 8.2), 7.45-7.36 (3H, m), 7.32-7.27 (3H, m), 7.20-7.13 (2H, m), 3.15 (2H, dq, J 7.2 and 6.1), 1.07 (311, t, J 7.2); [M+H]+ m/z=410.1

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. additionpoured onto water
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic phase was washed successively with water (20 mL), saturated aqueous sodium bicarbonate (20 mL) and brine (2×20 mL)
  5. dry with materialdried (MgSO4)
  6. customto give the crude product
  7. customThis was triturated with EtOAc

Sources & evidence

ORD record
ord-24bf44d02e2749c1a7bebe597f0622e9
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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