Diisopropylethylamine → N-[5-[({[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]amino]carbonyl)amino]-2-methylphenyl}-1-(2,6-dichlorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide

HRID 1921295Notes

Reaction equation

HRID 1921295 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:14](=[O:15])[CH:13]=[CH:12][C:11]([C:16]([OH:18])=O)=[CH:10]1.[NH2:19][C:20]1[CH:21]=[C:22]([NH:27][C:28]([NH:30][C:31]2[N:35]([C:36]3[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=3)[N:34]=[C:33]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:32]=2)=[O:29])[CH:23]=[CH:24][C:25]=1[CH3:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[C:43]([C:33]1[CH:32]=[C:31]([NH:30][C:28]([NH:27][C:22]2[CH:23]=[CH:24][C:25]([CH3:26])=[C:20]([NH:19][C:16]([C:11]3[CH:12]=[CH:13][C:14](=[O:15])[N:9]([C:3]4[C:4]([Cl:8])=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])[CH:10]=3)=[O:18])[CH:21]=2)=[O:29])[N:35]([C:36]2[CH:37]=[CH:38][C:39]([CH3:42])=[CH:40][CH:41]=2)[N:34]=1)([CH3:46])([CH3:45])[CH3:44]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 655011901-(2,6-Dichlorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarboxylic acidHCID 670568481-(3-amino-4-methylphenyl)-3-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]urea

Product 1

HCID 25115849N-[5-[({[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]amino]carbonyl)amino]-2-methylphenyl}-1-(2,6-dichlorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamideYield 42.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(2,6-dichlorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid (35 mg) and 1-(3-amino-4-methylphenyl)-3-[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]urea (70 mg) in DMF (1 mL) were added HATU (71 mg) and iPr2NEt (96 mg) successively under a nitrogen atmosphere, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with EtOAc (5 mL) and the resulted mixture was successively washed with 1M HCl (5 mL×2), saturated aqueous NaHCO3 (5 mL×2) and brine, dried over MgSO4, filtered and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with 5% MeOH in CH2Cl2. The isolated material was triturated with CH2Cl2, and the precipitates were collected by filtration to give N-[5-[({[3-tert-butyl-1-(4-methylphenyl)-1H-pyrazol-5-yl]amino]carbonyl)amino]-2-methylphenyl}-1-(2,6-dichlorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarboxamide (34 mg).

Workup

  1. washthe resulted mixture was successively washed with 1M HCl (5 mL×2), saturated aqueous NaHCO3 (5 mL×2) and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with 5% MeOH in CH2Cl2
  7. customThe isolated material was triturated with CH2Cl2
  8. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-2ad11379eafa432bb22e9bd506a30132
Source dataset
uspto-grants-2012_05
Patent number
US08173684B2

Reaction notes

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