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

HRID 490945노트

반응식

HRID 490945 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매4회

반응 조건

온도
0 °C

실험 절차

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 benzenesulfonyichloride (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.

후처리

  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

출처 및 근거

ORD 기록
ord-0770ad6415da4afebe0917c5e166b89d
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07528173B2

반응 노트

불러오는 중…