Ammonia → 6-(3-Ethylureido)-4-(phenylamino)nicotinamide

HRID 2174251Notes

Reaction equation

HRID 2174251 reaction equation
[NH:1]([C:8]1[CH:13]=[C:12]([NH:14][C:15](=[O:19])[NH:16][CH2:17][CH3:18])[N:11]=[CH:10][C:9]=1[C:20]([OH:22])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N:26](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(=[N+](C)C)N(C)C)C2C=CC=CC=2N=N1.N>CN(C=O)C.CO.C(Cl)Cl>[CH2:17]([NH:16][C:15](=[O:19])[NH:14][C:12]1[CH:13]=[C:8]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:9]([C:20]([NH2:26])=[O:22])=[CH:10][N:11]=1)[CH3:18]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896500056-(3-Ethylureido)-4-(phenylamino)nicotinic acid

Product 1

HCID 896503086-(3-Ethylureido)-4-(phenylamino)nicotinamideYield 8,918.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

4-anilino-6-(ethylcarbamoylamino)pyridine-3-carboxylic acid (i) (70 mg, 0.23 mmol) was suspended in DMF (2 mL) and N,N-diisopropylethyl amine (0.16 mL, 0.93 mmol) was added, causing the solid to dissolve. The [benzotriazol-1-yloxy(dimethylamino)methylene]-dimethyl-ammonium hexafluorophosphate (97 mg, 0.26 mmol) was added. After stirring at RT for 10 min, ammonia (1 mL, 25 mass %, 14.7 mmol) was added. The mixture was stirred overnight at RT. The mixture was quenched with NH4Cl and diluted with water and EtOAc. The mixture was extracted into EtOAc (3×20 mL), the organics combined and dried with brine then over MgSO4. The solvent was removed to afford a crude residue as a white solid. The solid was dissolved in MeOH/DCM and applied to a silica column, eluting with MeOH/DCM, to give Compound 6140 mg. 1H NMR (400 MHz, CD3OD) δ 8.46-8.39 (m, 1H), 7.44-7.37 (m, 2H), 7.29-7.23 (m, 2H), 7.22-7.14 (m, 1H), 6.84 (s, 1H), 3.29-3.24 (m, 2H), 1.18 (t, J=7.2 Hz, 3H).

Workup

  1. dissolutionto dissolve
  2. stirringThe mixture was stirred overnight at RT
  3. customThe mixture was quenched with NH4Cl
  4. additiondiluted with water and EtOAc
  5. extractionThe mixture was extracted into EtOAc (3×20 mL)
  6. dry with materialdried with brine
  7. customThe solvent was removed
  8. customto afford a crude residue as a white solid
  9. washeluting with MeOH/DCM

Sources & evidence

ORD record
ord-fa5f338dde0544ae92d2783d63c17ac8
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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