Diisopropylethylamine → Ethyl {3-[4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-3-oxopropyl}methylphosphinate

HRID 1013542Notes

Reaction equation

HRID 1013542 reaction equation
[CH2:1]([O:3][P:4]([CH2:7][CH2:8][C:9]([C:11]1[CH:19]=[CH:18][C:14]([C:15]([OH:17])=O)=[CH:13][CH:12]=1)=[O:10])([CH3:6])=[O:5])[CH3:2].[NH2:20][C:21]1[CH:26]=[C:25]([C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)[CH:24]=[CH:23][C:22]=1[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36].CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH3:38][C:35]([O:34][C:33]([NH:32][C:22]1[CH:23]=[CH:24][C:25]([C:27]2[S:28][CH:29]=[CH:30][CH:31]=2)=[CH:26][C:21]=1[NH:20][C:15]([C:14]1[CH:13]=[CH:12][C:11]([C:9](=[O:10])[CH2:8][CH2:7][P:4]([CH3:6])(=[O:5])[O:3][CH2:1][CH3:2])=[CH:19][CH:18]=1)=[O:17])=[O:39])([CH3:36])[CH3:37]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamateHCID 579259074-{3-[(Ethyloxy)(methyl)phosphoryl]propanoyl}benzoic acid

Product 1

HCID 57925974Ethyl {3-[4-({[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-3-oxopropyl}methylphosphinate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-{3-[(ethyloxy)(methyl)phosphoryl]propanoyl}benzoic acid (1 g, 3.52 mmol), 1,1-dimethylethyl [2-amino-4-(2-thienyl)phenyl]carbamate (1.532 g, 5.28 mmol), DIPEA (0.922 mL, 5.28 mmol) and BOP (2.334 g, 5.28 mmol) were stirred in DMF (10 mL) at room temperature overnight. Saturated NaHCO3 was added and the products extracted into EtOAc (×2). The combined organic extracts were washed with water and brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by MPLC (0-20% MeOH-EtOAc) gave ethyl {3-[4-({[2-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-3-oxopropyl}methylphosphinate as an orange solid. MS: cal'd 457 (MH+-Boc), exp 457 (MH+-Boc).

Workup

  1. extractionthe products extracted into EtOAc (×2)
  2. washThe combined organic extracts were washed with water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by MPLC (0-20% MeOH-EtOAc)
  6. customgave ethyl {3-[4-({[2-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]-3-oxopropyl}methylphosphinate as an orange solid

Sources & evidence

ORD record
ord-91c96a510e38439fac28de83780b889e
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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