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

HRID 2284790Notes

Reaction equation

HRID 2284790 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]#[C:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][C:19](=[O:31])[C@@H:20]([N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:21])[CH2:13]2)=[CH:4][N:3]=1.[NH2:32][C:33]1[CH:40]=[CH:39][C:36]([C:37]#[N:38])=[CH:35][CH:34]=1.[C@]12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.C(=O)([O-])O.[Na+]>CN1CCCC1=O.C(OCC)(=O)C>[C:37]([C:36]1[CH:39]=[CH:40][C:33]([NH:32][C:2]2[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]#[C:11][C@@H:12]3[CH2:17][CH2:16][CH2:15][C@H:14]([NH:18][C:19](=[O:31])[C@@H:20]([N:22]([CH3:30])[C:23](=[O:29])[O:24][C:25]([CH3:27])([CH3:28])[CH3:26])[CH3:21])[CH2:13]3)=[CH:4][N:3]=2)=[CH:34][CH:35]=1)#[N:38]

Participants

7

Reactant 4

HCID 133964-AminobenzonitrileHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 516892Sodium BicarbonateHCID 90052347tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

Product 1

HCID 90052364tert-butyl ((S)-1-(((1S,3R)-3-((2-((4-cyanophenyl)amino)-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl ((S)-1-(((1S,3R)-3-((2-chloro-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (Q4, 32 mg) in N-methylpyrrolidone (0.5 mL), 4-aminobenzonitrile (42 mg) and (1S)-(+)-10-camphorsulfonic acid (81 mg) were added at room temperature, and the mixture was stirred at 60° C. for 7 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, washed successively with saturated aqueous sodium hydrogencarbonate, water 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 25% hexane in ethyl acetate) to obtain tert-butyl ((S)-1-(((1S,3R)-3-((2-((4-cyanophenyl)amino)-4-methoxypyrimidin-5-yl)ethynyl)cyclohexyl)amino)-1-oxopropan-2-yl)(methyl)carbamate (Q5, 11 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed successively with saturated aqueous sodium hydrogencarbonate, water 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 25% hexane in ethyl acetate)

Sources & evidence

ORD record
ord-fffb83e3de8143bfb90ae90163702cef
Source dataset
uspto-grants-2015_09
Patent number
US09145415B2

Reaction notes

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