Isobutyl chloroformate → HCID 90052614, compound

HRID 2284716Notes

Reaction equation

HRID 2284716 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].ClC(OCC(C)C)=O.[F:19][C:20]1[CH:21]=[C:22]([NH:26][C:27]2[N:32]=[C:31]([NH:33][CH2:34][CH2:35][CH3:36])[C:30]([C:37]#[C:38][CH2:39][CH2:40][CH2:41][NH:42][C:43](=[O:48])[C@@H:44]([NH:46][CH3:47])[CH3:45])=[CH:29][N:28]=2)[CH:23]=[CH:24][CH:25]=1>CN(C)C=O.CN1CCOCC1.C(=O)([O-])O.[Na+]>[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7]([N:46]([C@@H:44]([CH3:45])[C:43]([NH:42][CH2:41][CH2:40][CH2:39][C:38]#[C:37][C:30]1[C:31]([NH:33][CH2:34][CH2:35][CH3:36])=[N:32][C:27]([NH:26][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([F:19])[CH:21]=2)=[N:28][CH:29]=1)=[O:48])[CH3:47])=[O:8]

Participants

7

Reactant 3

HCID 62365Isobutyl chloroformateHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 90051752HCID 90051752, compound

Product 1

HCID 90052614HCID 90052614, compoundYield 54.6%

Reagents, catalysts & solvents 3

HCID 516892Sodium BicarbonateCatalystHCID 6228DimethylformamideSolventHCID 79724-MethylmorpholineSolvent

Procedure

To a solution of 4-dimethylaminocrotonic acid hydrochloride (307 mg) in N,N-dimethylformamide (9 mL), N-methylmorpholine (682 μL) was added under ice cooling, and the mixture was stirred at the same temperature for 5 minutes. Then, isobutyl chloroformate (204 μL) was added to the mixture under ice cooling, and the mixture was stirred at the same temperature for 3 minutes. To the reaction mixture, (S)—N-(5-(2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)-2-(methylamino)propanamide (F6) dihydrochloride (300 mg) was added under ice cooling, and the mixture was stirred at the same temperature for 1 hour and 30 minutes. To the reaction mixture, saturated aqueous sodium hydrogencarbonate (10 drops) were 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) to obtain (S,E)-4-(dimethylamino)-N-(1-((5-(2-((3-fluorophenyl)amino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)-N-methyl-2-butenamide (7-1, 208 mg).

Workup

  1. stirringthe mixture was stirred at the same temperature for 3 minutes
  2. stirringthe mixture was stirred at the same temperature for 1 hour and 30 minutes
  3. customthe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by basic silica gel column chromatography (eluent, 100 to 90% ethyl acetate in methanol)

Sources & evidence

ORD record
ord-b7f2f46d14c64d259fe714b3022ab870
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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