Sodium hydride → Diethyl {2-[4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-1-cyanoethyl}phosphonate

HRID 1013467Notes

Reaction equation

HRID 1013467 reaction equation
[C:1]([CH2:3][P:4](=[O:11])([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])#[N:2].[H-].[Na+].Br[CH2:15][C:16]1[CH:43]=[CH:42][C:19]([C:20]([NH:22][C:23]2[CH:28]=[C:27]([C:29]3[S:30][CH:31]=[CH:32][CH:33]=3)[CH:26]=[CH:25][C:24]=2[NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:21])=[CH:18][CH:17]=1>C1COCC1.C(OCC)(=O)C>[C:37]([O:36][C:35]([NH:34][C:24]1[CH:25]=[CH:26][C:27]([C:29]2[S:30][CH:31]=[CH:32][CH:33]=2)=[CH:28][C:23]=1[NH:22][C:20]([C:19]1[CH:42]=[CH:43][C:16]([CH2:15][CH:3]([P:4](=[O:11])([O:8][CH2:9][CH3:10])[O:5][CH2:6][CH3:7])[C:1]#[N:2])=[CH:17][CH:18]=1)=[O:21])=[O:41])([CH3:40])([CH3:39])[CH3:38]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 57925962Tert-butyl [2-{[4-(bromomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate

Product 1

HCID 57925835Diethyl {2-[4-({[2-[(tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-1-cyanoethyl}phosphonate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Diethyl cyanomethylphosphonate (0.19 ml, 1.175 mmol) was dissolved in THF (7 ml). The solution was cooled to 0° C. Sodium hydride (0.0818 g, 2.045 mmol) was added to the reaction. The reaction was allowed to stir for several minutes. Tert-butyl [2-{[4-(bromomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate (0.5047 g, 1.035 mmol) was added in a solution of THF. The reaction was allowed to slowly warm to room temperature and stir overnight. The reaction was diluted with ethyl acetate and quenched with saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate three times. The combined organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting residue was partially purified by column chromatography on silica gel. MS: cal'd 484 (MH+-Boc), exp 484 (MH+-Boc).

Workup

  1. temperatureto slowly warm to room temperature
  2. stirringstir overnight
  3. customquenched with saturated aqueous ammonium chloride
  4. extractionThe aqueous layer was extracted with ethyl acetate three times
  5. dry with materialThe combined organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was partially purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-110ee8e2c6ce496f9a8df98e24943375
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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