1-Hydroxybenzotriazole → 6-(3-Ethylureido)-N-(1-methyl-1H-pyrazol-5-yl)-4-(phenylamino)nicotinamide

HRID 2174238Notes

Reaction equation

HRID 2174238 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].CN(C(O[N:31]1[N:39]=N[C:33]2[CH:34]=CC=[N:37][C:32]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:47]1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CN1C=CC(N)=N1>CN(C=O)C>[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]([NH:37][C:32]2[N:31]([CH3:47])[N:39]=[CH:34][CH:33]=2)=[O:12])=[CH:8][N:7]=1)[CH3:2]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1372541-Methyl-3-aminopyrazoleHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 896500056-(3-Ethylureido)-4-(phenylamino)nicotinic acid

Product 1

HCID 716208496-(3-Ethylureido)-N-(1-methyl-1H-pyrazol-5-yl)-4-(phenylamino)nicotinamideYield 25%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice-cold solution of 6-(3-ethylureido)-4-(phenylamino)nicotinic acid (50 mg, 0.16 mmol, 1.0 eq) in DMF (2.0 mL) was added HATU (0-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate, 91 mg, 0.24 mmol, 1.50 eq) followed by HOBt (N-hydroxybenzotriazole, 32 mg, 0.24 mmol, 1.50 eq), DIPEA (31 mg, 0.24 mmol, 1.50 eq) and finally the 1-methylpyrazol-3-amine (0.24 mmol, 23 mg, 1.50 eq). The resulting reaction mixture was stirred overnight at room temperature. The reaction mass was then poured onto the ice-cold water followed by extraction with EtOAc (3×20 mL). The reaction mass was then poured onto the 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 10 (15 mg, 25%). 1H NMR (300 MHz, DMSO-d6): δ 10.31 (br s, 1H), 9.97 (br s, 1H), 9.14 (br s, 1H), 8.64 (s, 1H), 7.85 (m, 1H), 7.40 (m, 3H), 7.27 (m, 3H), 7.17 (m, 1H), 6.23 (s, 1H), 3.71 (s, 3H), 3.13 (m, 2H) and 1.07 (m, 3H); [M+H]+ m/z=380.

Workup

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

Sources & evidence

ORD record
ord-ac30d5efad0b461e88156e74a4bad3d2
Source dataset
uspto-grants-2015_06
Patent number
US09060515B2

Reaction notes

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