Tetrafluoro-m-phenylenediamine dihydrochloride → HCID 90052299, compound

HRID 2284761Notes

Reaction equation

HRID 2284761 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].[F:11][C:12]1[CH:13]=[C:14]([NH:18][C:19]2[N:24]=[C:23]([NH:25][CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:22]([C:31]#[C:32][CH2:33][CH2:34][CH2:35][NH:36][C:37](=[O:42])[C@@H:38]([NH:40][CH3:41])[CH3:39])=[CH:21][N:20]=2)[CH:15]=[CH:16][CH:17]=1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>CN(C)C=O.CN1CCOCC1.ClC(OCC(C)C)=O.C(=O)([O-])O.[Na+]>[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7]([N:40]([C@@H:38]([CH3:39])[C:37]([NH:36][CH2:35][CH2:34][CH2:33][C:32]#[C:31][C:22]1[C:23]([NH:25][CH2:26][CH2:27][CH2:28][O:29][CH3:30])=[N:24][C:19]([NH:18][C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([F:11])[CH:13]=2)=[N:20][CH:21]=1)=[O:42])[CH3:41])=[O:8]

Participants

8

Reactant 3

HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 90052300HCID 90052300, compound

Product 1

HCID 90052299HCID 90052299, compound

Reagents, catalysts & solvents 4

HCID 516892Sodium BicarbonateCatalystHCID 6228DimethylformamideSolventHCID 79724-MethylmorpholineSolventHCID 62365Isobutyl chloroformateSolvent

Procedure

To a solution of 4-dimethylaminocrotonic acid hydrochloride (61 mg) in N,N-dimethylformamide (0.5 mL), N-methylmorpholine (135 μL) and isobutyl chloroformate (40 μL) were added under ice cooling, then (S)—N-(5-(2-((3-fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)-2-(methylamino)propanamide (J9) dihydrochloride (55 mg) was further added, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture, saturated aqueous sodium hydrogencarbonate (10 drops) was added, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography to obtain (S,E)-4-(dimethylamino)-N-(1-((5-(2-((3-fluorophenyl)amino)-4-((3-methoxypropyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)-N-methyl-2-butenamide (10-1, 45 mg).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe obtained residue was purified by basic silica gel column chromatography

Sources & evidence

ORD record
ord-d4bd6605deaf4488bbcef3e20700ecf0
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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