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Diisopropylethylamine → 2-[4-({[2-[(Tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]ethyl ethyl methylphosphonate

HRID 1013522
Notes
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Reaction equation

HRID 1013522 reaction equation
OC[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.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH2:58]([O:60][P:61]([O:64][CH2:65][CH2:66]C1C=CC(C(O)=O)=CC=1)([CH3:63])=[O:62])[CH3:59].CCN(C(C)C)C(C)C>CN(C=O)C.C([O-])(O)=O.[Na+]>[CH3:63][P:61](=[O:62])([O:64][CH2:65][CH3:66])[O:60][CH2:58][CH2:59][C:3]1[CH:4]=[CH:5][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:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:30])=[O:10])=[CH:7][CH:8]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 57607813Tert-butyl 2-{[4-(hydroxymethyl)benzoyl]amino}-4-thien-2-ylphenylcarbamateHCID 579259664-(2-{[Ethoxy(methyl)phosphoryl]oxy}ethyl)benzoic acid

Product 1

HCID 57925964
2-[4-({[2-[(Tert-butoxycarbonyl)amino]-5-(2-thienyl)phenyl]amino}carbonyl)phenyl]ethyl ethyl methylphosphonate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

1,1-dimethylethyl [2-({[4-(hydroxymethyl)phenyl]carbonyl}amino)-4-(2-thienyl)phenyl]carbamate (140 mg, 0.50 mmol), BOP (440 mg, 0.99 mmol), 4-(2-{[ethoxy(methyl)phosphoryl]oxy}ethyl)benzoic acid (90 mg, 0.33 mmol), and DIPEA (0.17 mL, 0.99 mmol) were stirred in DMF (1.1 mL) at 60° C. for 72 hours. The mixture was then diluted with saturated NaHCO3 solution and extracted with EtOAc. The organic layers were then washed with brine, dried over Na2SO4 and concentrated in vacuo. Purification of the crude reaction mixture by MPLC (0-10% MeOH/DCM) resulted in the title compound as a yellow foam. MS cal'd 445 (MH+-Boc), exp 445 (MH+-Boc).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layers were then washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customPurification of the crude
  6. customreaction mixture by MPLC (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-8087cdb1fc6e43bea7b6e8bba7d9b57a
Source dataset
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07981874B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes