Tetrahydrofuran → 4-(Dimethylphosphoryl)benzyl(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}benzyl) carbamate

HRID 1013532Notes

Reaction equation

HRID 1013532 reaction equation
C1N=CN([C:6](N2C=NC=C2)=[O:7])C=1.[CH3:13][P:14]([C:17]1[CH:22]=[CH:21][C:20]([CH2:23]O)=[CH:19][CH:18]=1)([CH3:16])=[O:15].NC[C:27]1[CH:32]=[CH:31][C:30]([C:33]([NH:35][C:36]2[CH:37]=[C:38]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[CH:39]=[CH:40][C:41]=2[NH:42]C(=O)OC(C)(C)C)=[O:34])=[CH:29][CH:28]=1.CC[N:58]([CH2:61]C)CC.C1CCN2C(=NCCC2)CC1.C1C[O:77]CC1>CS(C)=O>[C:61](=[O:77])([O:7][CH:6]([CH2:23][C:20]1[CH:19]=[CH:18][C:17]([P:14]([CH3:13])([CH3:16])=[O:15])=[CH:22][CH:21]=1)[C:27]1[CH:32]=[CH:31][C:30]([C:33]([NH:35][C:36]2[CH:37]=[C:38]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[CH:39]=[CH:40][C:41]=2[NH2:42])=[O:34])=[CH:29][CH:28]=1)[NH2:58]

Participants

8

Reactant 6

HCID 8028Tetrahydrofuran3×HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 57925864N-[3-[[4-(Aminomethyl)benzoyl]amino][1,1'-biphenyl]-4-yl]carbamic Acid tert-Butyl EsterHCID 591314474-(Dimethylphosphinyl)benzenemethanol

Product 1

HCID 673167454-(Dimethylphosphoryl)benzyl(4-{[(4-aminobiphenyl-3-yl)amino]carbonyl}benzyl) carbamate

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of CDI (117 mg, 0.722 mmol) in dry THF (5 mL) was treated with a solution of [4-(dimethylphosphoryl)phenyl]methanol (133 mg, 0.722 mmol) in DMSO (2 mL) and THF (1 mL) dropwise. The resulting solution was stirred for 1 h and then added dropwise over 5 min. to a solution of 1,1-dimethylethyl [3-({[4-(aminomethyl)phenyl]carbonyl}amino) biphenyl-4-yl]carbamate (301 mg, 0.722 mmol), Et3N (101 μL, 0.722 mmol) and DBU (109 μL, 0.722 mmol) in dry THF (5 mL). The reaction mixture was stirred at RT overnight. The reaction mixture was concentrated in vacuo, diluted with EtOAc, washed with H2O, 0.5 N HCl, dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with CHCl3/MeOH (2.5% to 20%) to give a glassy yellow solid. 1H NMR (CDCl3, 600 MHz) δ 9.28 (br s, 1H), 8.02 (s, 1H), 7.90 (d, J=8.0 Hz, 2H), 7.75-7.67 (m, 2H), 7.59 (d, J=8.0 Hz, 2H), 7.50-7.46 (m, 2H), 7.42-7.35 (m, 4H), 7.34-7.29 (m, 1H), 7.27 (d, J=8.0 Hz, 2H), 6.98 (s, 1H), 5.49 (br s, 1H), 5.18 (s, 2H), 4.41 (d, J=6.0 Hz, 2H), 1.71 (dd. J=12.9, 3.8 Hz, 6H). MS: cal'd 628 (MH+), exp 628 (MH+).

Workup

  1. stirringThe reaction mixture was stirred at RT overnight
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiondiluted with EtOAc
  4. washwashed with H2O, 0.5 N HCl
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel
  9. washeluting with CHCl3/MeOH (2.5% to 20%)
  10. customto give a glassy yellow solid

Sources & evidence

ORD record
ord-3dfd0b1e5d3c4f48ad498d844bdce0f0
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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