Tetrafluoro-m-phenylenediamine dihydrochloride → HCID 90051776, compound

HRID 2284752Notes

Reaction equation

HRID 2284752 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:13]([C:21]#[C:22][CH2:23][CH2:24][CH2:25][NH:26][C:27](=[O:32])[C@@H:28]([NH:30][CH3:31])[CH3:29])=[CH:12][N:11]=2)=[CH:5][CH:4]=1)#[N:2].C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.Cl.[CH3:48][N:49]([CH3:56])[CH2:50]/[CH:51]=[CH:52]/[C:53](O)=[O:54]>CN(C)C=O.CN1CCOCC1.ClC(OCC(C)C)=O.C(=O)([O-])O.[Na+]>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]2[N:15]=[C:14]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:13]([C:21]#[C:22][CH2:23][CH2:24][CH2:25][NH:26][C:27](=[O:32])[C@@H:28]([N:30]([CH3:31])[C:53](=[O:54])/[CH:52]=[CH:51]/[CH2:50][N:49]([CH3:56])[CH3:48])[CH3:29])=[CH:12][N:11]=2)=[CH:7][CH:8]=1)#[N:2]

Participants

8

Reactant 3

HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 90051778HCID 90051778, compound

Product 1

HCID 90051776HCID 90051776, compound

Reagents, catalysts & solvents 4

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

Procedure

To a solution of (S)—N-(5-(2-((4-cyanophenyl)amino)-4-(pyrrolidin-1-yl)pyrimidin-5-yl)-4-pentyn-1-yl)-2-(methylamino)propanamide (H6) dihydrochloride (252 mg) and 4-dimethylaminocrotonic acid hydrochloride (331 mg) in N,N-dimethylformamide (8 mL), N-methylmorpholine (660 μL) and isobutyl chloroformate were added under ice cooling, and the mixture was stirred at the same temperature for 1 hour. To the reaction mixture, saturated aqueous sodium hydrogencarbonate (5 drop) was added, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent, 100 to 90% ethyl acetate in methanol). The obtained solid matter was washed with a mixed solvent of ethyl acetate and hexane, and then dried under reduced pressure to obtain (S,E)-N-(1-((5-(2-((4-cyanophenyl)amino)-4-(pyrrolidin-1-yl)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)-4-(dimethylamino)-N-methyl-2-butenamide (9-1, 132 mg) as white solid.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 100 to 90% ethyl acetate in methanol)
  3. washThe obtained solid matter was washed with a mixed solvent of ethyl acetate and hexane
  4. customdried under reduced pressure

Sources & evidence

ORD record
ord-6e82af737c2749dc8c6da26f8c9d7212
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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