Hydrochloric Acid → {[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-2-methyl-biphenyl-4-ylamino]-methyl}-phosphonic acid

HRID 2216088Notes

Reaction equation

HRID 2216088 reaction equation
C([O:3][P:4]([CH2:9][NH:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([S:23]([C:26]3[CH:30]=[C:29]([C:31]([NH:33]C(OC(C)(C)C)=O)=[NH:32])[S:28][C:27]=3[S:41][CH3:42])(=[O:25])=[O:24])[CH:18]=2)=[C:13]([CH3:43])[CH:12]=1)(=[O:8])[O:5]CC)C.I[Si](C)(C)C.Cl.C(O)(C(F)(F)F)=O.C(Cl)Cl>C(Cl)Cl.CO.O>[C:31]([C:29]1[S:28][C:27]([S:41][CH3:42])=[C:26]([S:23]([C:19]2[CH:18]=[C:17]([C:14]3[CH:15]=[CH:16][C:11]([NH:10][CH2:9][P:4](=[O:3])([OH:8])[OH:5])=[CH:12][C:13]=3[CH3:43])[CH:22]=[CH:21][CH:20]=2)(=[O:25])=[O:24])[CH:30]=1)(=[NH:32])[NH2:33]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 85247Trimethylsilyl iodideHCID 21863450Trifluoroacetic acid methylene chlorideHCID 145857691tert-butyl N-[4-[3-[4-(diethoxyphosphorylmethylamino)-2-methylphenyl]phenyl]sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate

Product 1

HCID 21886119{[3'-(5-Carbamimidoyl-2-methylsulfanyl-thiophene-3-sulfonyl)-2-methyl-biphenyl-4-ylamino]-methyl}-phosphonic acidYield 38%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of ({3′-[5-(tert-butoxycarbonylamino-imino-methyl)-2-methylsulfanyl-thiophene-3-sulfonyl]-2-methyl-biphenyl-4-yl amino}-methyl) phosphonic acid diethyl ester (38 mg, 0.057 mmol) in DCM (1.2 mL) at 0° C. was added iodotrimethylsilane (25 μL) over 3 minutes period. After 1 h at 0° C., H2O was added. The mixture was stirred for 30 minutes, and then concentrated to give a brown solid. The solid was dissolved in MeOH (1.32 mL), 20% HCl was added, and stirred at ambient temperature for 3 h. The mixture was concentrated to give a brown solid. To this solid was added TFA/DCM (1:1, 3 mL) and stirred at ambient temperature for 40 minutes. The reaction mixture was then concentrated and purified by HPLC (C18 column, 10–70% CH3CN over 30 minutes) to give the title compound (11 mg, 38% yield) as a white solid.

Workup

  1. concentrationconcentrated
  2. customto give a brown solid
  3. stirringstirred at ambient temperature for 3 h
  4. concentrationThe mixture was concentrated
  5. customto give a brown solid
  6. stirringstirred at ambient temperature for 40 minutes
  7. concentrationThe reaction mixture was then concentrated
  8. custompurified by HPLC (C18 column, 10–70% CH3CN over 30 minutes)

Sources & evidence

ORD record
ord-a2cd9bca919f4fc9a67b4ab727ac39d2
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

Loading…