Water → HCID 118061451, compound

HRID 632786Notes

Reaction equation

HRID 632786 reaction equation
[NH2:1][C@@H:2]1[CH2:6][N:5]([C:7]2[C:11]([NH:12][C:13]([C:15]3[N:16]=[C:17]([C:20]4[CH:25]=[CH:24][N:23]=[C:22]([N:26]([CH2:34][C:35]([F:38])([F:37])[F:36])C(=O)OC(C)(C)C)[CH:21]=4)[O:18][CH:19]=3)=[O:14])=[CH:10][N:9]([CH3:39])[N:8]=2)[C:4](=[O:40])[CH2:3]1.C(=O)([O-])O.[Na+].[CH2:46]([O:49][CH2:50][CH2:51]Br)[CH2:47]Br.O>C1(C)C=CC=CC=1>[CH3:39][N:9]1[CH:10]=[C:11]([NH:12][C:13]([C:15]2[N:16]=[C:17]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][CH2:34][C:35]([F:36])([F:37])[F:38])[CH:21]=3)[O:18][CH:19]=2)=[O:14])[C:7]([N:5]2[CH2:6][C@@H:2]([N:1]3[CH2:51][CH2:50][O:49][CH2:46][CH2:47]3)[CH2:3][C:4]2=[O:40])=[N:8]1

Participants

6

Reactant 4

HCID 962WaterHCID 21521Bis(2-bromoethyl) etherHCID 516892Sodium BicarbonateHCID 131735451HCID 131735451, compound

Product 1

HCID 118061451HCID 118061451, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl (4-(4-((3-((4S)-4-amino-2-oxopyrrolidin-1-yl)-1-methyl-1H-pyrazol-4-yl)carbamoyl)-1,3-oxazol-2-yl)pyridin-2-yl)(2,2,2-trifluoroethyl)carbamate (79 mg) and sodium hydrogen carbonate (70 mg) in toluene (0.70 mL) was added 2,2′-dibromodiethyl ether (0.035 mL), and the mixture was stirred overnight at 100° C. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in TFA (0.70 mL), and the solution was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate), and recrystallized from ethyl acetate/hexane to give the title compound (3.3 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in TFA (0.70 mL)
  6. stirringthe solution was stirred at room temperature for 30 min
  7. concentrationThe reaction mixture was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate)
  9. customrecrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-cf7d67a84c144f4fb34fc572334e19cc
Source dataset
uspto-grants-2016_04
Patent number
US09321757B2

Reaction notes

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