Hydrochloric Acid → tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

HRID 2284789Notes

Reaction equation

HRID 2284789 reaction equation
[C:1]([N:8]([CH3:14])[C@H:9]([C:11]([OH:13])=O)[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Cl:15][C:16]1[N:21]=[C:20]([O:22][CH3:23])[C:19]([C:24]#[C:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][C@H:28]([NH2:32])[CH2:27]2)=[CH:18][N:17]=1.Cl.C(=O)([O-])O.[Na+]>CN(C)C=O.CN1CCOCC1.ClC(OCC(C)C)=O.C(OCC)(=O)C>[Cl:15][C:16]1[N:21]=[C:20]([O:22][CH3:23])[C:19]([C:24]#[C:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][C@H:28]([NH:32][C:11](=[O:13])[C@@H:9]([N:8]([CH3:14])[C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7])[CH3:10])[CH2:27]2)=[CH:18][N:17]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 7009590(2S)-2-(((tert-butoxy)carbonyl)(methyl)amino)propanoic acidHCID 90052507(1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexaneamine

Product 1

HCID 90052347tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolvent2×HCID 79724-MethylmorpholineSolventHCID 8857Ethyl AcetateSolventHCID 62365Isobutyl chloroformateSolvent

Procedure

To a solution of N-Boc-N-methyl-L-alanine (195 mg) in N,N-dimethylformamide (2.5 mL), N-methylmorpholine (246 μL) and isobutyl chloroformate (105 μL) were added under ice cooling, and the mixture was stirred at the same temperature for 2 minutes. To the reaction mixture, a solution of (1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexaneamine (Q3) hydrochloride in N,N-dimethylformamide (2 mL) 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 and ethyl acetate were added. The organic layer was separated, washed successively with water, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 88 to 40% hexane in ethyl acetate) to obtain tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (Q4, 120 mg).

Workup

  1. stirringthe mixture was stirred at the same temperature for 1 hour and 30 minutes
  2. customThe organic layer was separated
  3. washwashed successively with water, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent, 88 to 40% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-d2f40397b4084f23b0e1da5b2fdddefd
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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