Benzenesulfonyl chloride → 2-(3-(Amino)methylphenyl)-3-((1-(phenylsulfonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid

HRID 1677624Notes

Reaction equation

HRID 1677624 reaction equation
C[O:2][C:3](=[O:31])[CH:4]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][NH:23]C(OC(C)(C)C)=O)[CH:17]=1)[CH2:5][P:6]([CH:11]([NH2:15])[CH:12]([CH3:14])[CH3:13])([O:8]CC)=[O:7].CCN(C(C)C)C(C)C.[C:41]1([S:47](Cl)(=[O:49])=[O:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C[Si](Br)(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[NH2:23][CH2:22][C:18]1[CH:17]=[C:16]([CH:4]([CH2:5][P:6]([CH:11]([NH:15][S:47]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)(=[O:49])=[O:48])[CH:12]([CH3:13])[CH3:14])([OH:8])=[O:7])[C:3]([OH:2])=[O:31])[CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 76113BromotrimethylsilaneHCID 81531DiisopropylethylamineHCID 673750552-(3-(t-Butoxycarbonylamino)methylphenyl)-3-((1-amino-2-methylpropyl)(ethoxy)-phosphinoyl)propanoic acid methyl ester

Product 1

HCID 119789532-(3-(Amino)methylphenyl)-3-((1-(phenylsulfonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acidYield 44%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(3-(t-butoxycarbonylamino)methylphenyl)-3-((1-amino-2-methylpropyl)(ethoxy)phosphinoyl)propanoic acid methyl ester (344 mg, 0.75 mmol) in methylene chloride (10 mL) was added DIEA (394 μL, 2.25 mmol) followed by DMAP (3.4 mg (cat.)). The reaction mixture was cooled to 0° C. and a solution of benzenesulfonylchloride (200 mg, 1.13 mmol) in methylene chloride was added dropwise over 15 minutes. The reaction mixture was stirred at 0° C. for 30 minutes and allowed to warm to ambient temperature overnight. The reaction was diluted with methylene chloride and washed with 2 N aq NaHSO4, water, brine and dried over sodium sulfate. Evaporation gave a crude residue (425 mg) that was dissolved in 2.5 mL of methylene chloride and cooled to 0° C. under N2. TMSBr (1 mL) was added dropwise and the reaction was stirred at ambient temperature overnight, quenched with MeOH and evaporated. The resulting residue was dissolved in 5 mL of MeOH/H2O (1:1), neutralized with 0.25 M aq LiOH and 300 mg of LiOH and 10 mL of H2O. The reaction mixture was stirred at ambient temperature overnight. The solvents were evaporated and purification by preparative HPLC yielded 150 mg of 2-(3-(amino)methylphenyl)-3-((1-(phenylsulfonyl)amino-2-methylpropyl)(hydroxy)-phosphinoyl)propanoic acid, NMR (DMSO-d6) 0.5-0.8 (m, 6), 1.8 (m, 1), 1.92 (m, 1), 2.35 (m, 1) 3.25 (m, 1), 3.82 (m, 1), 4.0 (s, 2), 7.2 (dd, 1), 7.25-7.4 (m, 3), 7.4-7.6 (m, 3), 7.8 (m, 3), 8.18 (s, 3) ppm.

Workup

  1. temperatureto warm to ambient temperature overnight
  2. washwashed with 2 N aq NaHSO4, water, brine
  3. dry with materialdried over sodium sulfate
  4. customEvaporation
  5. customgave a crude residue (425 mg) that
  6. temperaturecooled to 0° C. under N2
  7. stirringthe reaction was stirred at ambient temperature overnight
  8. customquenched with MeOH
  9. customevaporated
  10. dissolutionThe resulting residue was dissolved in 5 mL of MeOH/H2O (1:1)
  11. stirringThe reaction mixture was stirred at ambient temperature overnight
  12. customThe solvents were evaporated
  13. custompurification by preparative HPLC

Sources & evidence

ORD record
ord-929ec1565599429b9902962f75de7a45
Source dataset
uspto-grants-2011_08
Patent number
US08008325B2

Reaction notes

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