Ethyl Acetate → (S)-tert-butyl methyl(1-oxo-1-((5-(2-(phenylamino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)propan-2-yl)carbamate

HRID 2284775Notes

Reaction equation

HRID 2284775 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH3:11])[C:5]([C:12]#[C:13][CH2:14][CH2:15][CH2:16][NH:17][C:18](=[O:30])[C@@H:19]([N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH3:20])=[CH:4][N:3]=1.[C@:31]12(CS(O)(=O)=O)C(C)(C)[CH:35]([CH2:36][CH2:37]1)[CH2:34][C:32]2=O.C(=O)([O-])O.[Na+].C(OCC)(=O)C.C[N:58]1CCCC1=O>NC1C=CC=CC=1>[CH3:29][N:21]([C@@H:19]([CH3:20])[C:18](=[O:30])[NH:17][CH2:16][CH2:15][CH2:14][C:13]#[C:12][C:5]1[C:6]([NH:8][CH2:9][CH2:10][CH3:11])=[N:7][C:2]([NH:58][C:32]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:31]=2)=[N:3][CH:4]=1)[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 5

HCID 8857Ethyl AcetateHCID 13387N-methyl-2-pyrrolidoneHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 516892Sodium BicarbonateHCID 90052304(S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate

Product 1

HCID 117856996(S)-tert-butyl methyl(1-oxo-1-((5-(2-(phenylamino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)propan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6115AnilineSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (S)-tert-butyl (1-((5-(2-chloro-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)-1-oxopropan-2-yl)(methyl)carbamate (L1, 57 mg) and (1S)-(+)-10-camphorsulfonic acid (150 mg) in N-methylpyrrolidone (1 mL), aniline (60 μL) was added at room temperature, and the mixture was stirred at 60° C. for 2 hours and 30 minutes. The reaction mixture was cooled to room temperature, and then saturated aqueous sodium hydrogencarbonate and ethyl acetate were added to the reaction mixture. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed successively with water and saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent, 50 to 25% hexane in ethyl acetate) to obtain oily (S)-tert-butyl methyl(1-oxo-1-((5-(2-(phenylamino)-4-(propylamino)pyrimidin-5-yl)-4-pentyn-1-yl)amino)propan-2-yl)carbamate (L2, 52 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washwashed successively with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (eluent, 50 to 25% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-b546c74f99af4900bc3ad6b75427d551
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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