Water → Diethyl [({[4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}amino)methyl)phosphonate

HRID 1013536Notes

Reaction equation

HRID 1013536 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:11][C:12]2[CH:17]=[C:16]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)[CH:15]=[CH:14][C:13]=2[NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:10])=[CH:5][CH:4]=1.C(O)(=O)C(O)=O.[NH2:37][CH2:38][P:39](=[O:46])([O:43][CH2:44][CH3:45])[O:40][CH2:41][CH3:42].CCN(C(C)C)C(C)C.O>CN(C=O)C>[CH3:29][C:26]([O:25][C:24]([NH:23][C:13]1[CH:14]=[CH:15][C:16]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)=[CH:17][C:12]=1[NH:11][C:9]([C:6]1[CH:5]=[CH:4][C:3]([CH2:2][NH:37][CH2:38][P:39](=[O:46])([O:43][CH2:44][CH3:45])[O:40][CH2:41][CH3:42])=[CH:8][CH:7]=1)=[O:10])=[O:30])([CH3:27])[CH3:28]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2733594diethyl (aminomethyl)phosphonate oxalate saltHCID 57925962Tert-butyl [2-{[4-(bromomethyl)benzoyl]amino}-4-(2-thienyl)phenyl]carbamate

Product 1

HCID 57925892Diethyl [({[4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}amino)methyl)phosphonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,1-dimethylethyl [2-({[4-(bromomethyl)phenyl]carbonyl}amino)-4-(2-thienyl)phenyl]carbamate (500 mg, 1.026 mmol), diethyl (aminomethyl)phosphonate oxalate (791 mg, 3.08 mmol), and DIPEA (1.254 mL, 7.18 mmol) were stirred in DMF (6 mL) at 50° C. overnight. Room temperature was attained, H2O: was added and the products extracted into EtOAc (×2). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by MPLC (0-10% MeOH-EtOAc) gave diethyl [({[4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]methyl}amino)methyl)phosphonate as a colourless gum. MS: cal'd 574 (MH+), exp 574.

Workup

  1. customRoom temperature
  2. extractionthe products extracted into EtOAc (×2)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by MPLC (0-10% MeOH-EtOAc)

Sources & evidence

ORD record
ord-bcdfd4dbab7a413b8b2cfc3e04b8015a
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

Loading…