Ethylamine → N-Ethyl-6-(3-ethylureido)-4-(phenylamino)nicotinamide

HRID 2174236Notes

Reaction equation

HRID 2174236 reaction equation
[CH2:1]([NH:3][C:4](=[O:22])[NH:5][C:6]1[CH:14]=[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:9]([C:10]([OH:12])=O)=[CH:8][N:7]=1)[CH3:2].[CH3:23][CH2:24][N:25]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N)C>C1COCC1.CN(C1C=CN=CC=1)C>[CH2:24]([NH:25][C:10](=[O:12])[C:9]1[C:13]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:14][C:6]([NH:5][C:4]([NH:3][CH2:1][CH3:2])=[O:22])=[N:7][CH:8]=1)[CH3:23]

Participants

7

Reactant 4

HCID 6341EthylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 896500056-(3-Ethylureido)-4-(phenylamino)nicotinic acid

Product 1

HCID 71620847N-Ethyl-6-(3-ethylureido)-4-(phenylamino)nicotinamideYield 92%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(3-ethylureido)-4-(phenylamino)nicotinic acid (50 mg, 0.16 mmol, 1.0 eq) in THF (5.0 mL) was added EDCI.HCl (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, 46 mg, 0.24 mmol, 1.50 eq) followed by HOBt (N-hydroxybenzotriazole, 32 mg, 0.24 mmol, 1.50 eq), DMAP (4-dimethylaminopyridine, 29 mg, 0.24 mmol, 1.50 eq) and finally, ethyl amine (16 mg 70% solution, 0.24 mmol, 1.50 eq). The resulting reaction mixture was stirred overnight at room temperature. The reaction mass was then poured onto ice-cold water followed by extraction with EtOAc (3×20 mL). The organics were combined, washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified over silica gel (60-120 M, 1-2.5% MeOH-DCM) to obtain Compound 8 (48 mg, 92%), 1H NMR (300 MHz, DMSO-d6): δ 10.43 (br s, 1H), 9.03 (br s, 1H), 8.52 (t, J=5.20 Hz, 1H), 8.41 (5, 1H), 7.94 (br s, 1H), 7.39 (m, 2H), 7.22 (m, 3H), 7.13 (m, 1H), 3.26 (m, 2H), 3.13 (m, 2H), 1.12 (t, J=7.20 HZ, 3H) and 1.05 (t, J=7.20 Hz, 3H). [M+H]+ m/z=328.18.

Workup

  1. customThe resulting reaction mixture
  2. additionThe reaction mass was then poured onto ice-cold water
  3. extractionfollowed by extraction with EtOAc (3×20 mL)
  4. washwashed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified over silica gel (60-120 M, 1-2.5% MeOH-DCM)

Sources & evidence

ORD record
ord-aa48b522cec64654807fb3dd3f6253ba
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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