Trimethyl phosphite → HCID 57925890, compound

HRID 1013461Notes

Reaction equation

HRID 1013461 reaction equation
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][C:9]=1[NH:19][C:20](=[O:29])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[CH:23][CH:22]=1)(C)(C)C.[CH3:31][O:32][P:33]([O:36]C)[O:34][CH3:35]>C1(C)C=CC=CC=1.CCOC(C)=O>[CH3:31][O:32][P:33]([CH2:27][C:24]1[CH:23]=[CH:22][C:21]([C:20](=[O:29])[NH:19][C:9]2[CH:10]=[C:11]([C:14]3[S:15][CH:16]=[CH:17][CH:18]=3)[CH:12]=[CH:13][C:8]=2[NH2:7])=[CH:26][CH:25]=1)(=[O:36])[O:34][CH3:35]

Participants

5

Reactant 2

HCID 8472Trimethyl phosphiteHCID 57925962Tert-butyl [2-{[4-(bromomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate

Product 1

HCID 57925890HCID 57925890, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

[2-(4-Bromomethyl-benzoylamino)-4-thiophen-2-yl-phenyl]-carbamic acid tert-butyl ester (0.20 g, 0.41 mmol) was made 2.0 M in anhydrous toluene and to this stirring solution was added trimethylphosphite (0.06 g, 0.45 mmol). The resulting reaction mixture was sealed and stirred at 100° C. for 18 h. The reaction mixture was diluted with EtOAc and washed with saturated aqueous sodium bicarbonate. The organic layer was further washed with brine then dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DMF:MeOH and purified by HPLC (45-95% MeCN in water w/0.025% TFA). Pure fractions were identified, combined, and concentrated in vacuo. The residue was dissolved in 2:1 DCM:TFA and stirred at ambient temperature. After 1 hour the mixture was concentrated in vacuo, diluted with EtOAc, washed with saturated aqueous sodium bicarbonate, brine, dried (MgSO4), then concentrated in vacuo to give the title compound: 1H NMR (DMSO-d6, 600 MHz) 9.68 (s, 1H), 7.92 (d, J=8.4 Hz, 2H), 7.45 (s, 1H), 7.37-7.41 (m, 2H), 7.32-7.34 (m, 1H), 7.26-7.29 (m, 1H), 7.21-7.23 (m, 1H), 7.01-7.04 (m, 1H), 6.78 (d, J=8.4 Hz, 2H), 5.14 (s, 2H), 3.60 (d, J=11.4 Hz, 6H), 3.37 (d, J=22.2 Hz, 2H). MS: cal'd 417 (MH+), exp 417 (MH+)

Workup

  1. customThe resulting reaction mixture
  2. customwas sealed
  3. washwashed with saturated aqueous sodium bicarbonate
  4. washThe organic layer was further washed with brine
  5. dry with materialthen dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in DMF
  8. customMeOH and purified by HPLC (45-95% MeCN in water w/0.025% TFA)
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in 2:1 DCM
  11. stirringTFA and stirred at ambient temperature
  12. concentrationAfter 1 hour the mixture was concentrated in vacuo
  13. additiondiluted with EtOAc
  14. washwashed with saturated aqueous sodium bicarbonate, brine
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-629d45b246e44964b031957541af3805
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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