Triethylamine → 1,1,1,3,3,3-Hexafluoro-2-(4-(4-(3-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

HRID 1972346노트

반응식

HRID 1972346 반응식
[F:1][C:2]([F:22])([F:21])[C:3]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].C(N(CC)CC)C.[S:30]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31]1>ClCCCl>[F:22][C:2]([F:1])([F:21])[C:3]([C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH2:20][CH2:19][N:18]([S:35]([C:32]3[CH:33]=[CH:34][S:30][CH:31]=3)(=[O:37])=[O:36])[CH2:17][CH2:16]2)=[CH:13][CH:14]=1)([OH:8])[C:4]([F:7])([F:6])[F:5]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 2776378Thiophene-3-sulfonyl ChlorideHCID 866237611,1,1,3,3,3-Hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol

생성물 1

HCID 866703021,1,1,3,3,3-Hexafluoro-2-(4-(4-(3-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

To a solution of 1,1,1,3,3,3-hexafluoro-2-(4-(1-piperazinyl)phenyl)-2-propanol (50 mg, 0.152 mmol, published PCT patent application no. WO 2006/094842) and triethylamine (63.6 μL, 0.457 mmol) in 1,2-dichloroethane (1.5 mL) was added 3-thiophenesulfonyl chloride (1M in dichloroethane, 168 μL, 0.168 mmol, ASDI, Newark, Del.). The reaction was shaken on an orbital shaker for 18 h. The reaction solvent was removed under reduced pressure and the crude product was purified by reverse-phase preparative HPLC using a Sunfire Prep C18 OBD (100×19 mm, 5 μm) column, 0.1% TFA in MeOH/H2O, gradient (65% to 95% over 4.5 min) to provide 1,1,1,3,3,3-hexafluoro-2-(4-(4-(3-thiophenylsulfonyl)-1-piperazinyl)phenyl)-2-propanol. 1H NMR (400 MHz, DMSO-d6) δ 8.35-8.27 (m, 1H), 7.85 (dd, J=5.1, 2.9 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.37 (d, J=5.1 Hz, 1H), 7.02 (d, J=9.0 Hz, 2H), 3.33-3.28 (m, 4H), 3.07-3.01 (m, 4H). m/z (ESI, +ve ion) 475.1 (M+H)+. GK-GKRP EC50 (NADPH-coupled)=0.597 μM; GK-GKRP EC50 (LC MS/MS)=0.964 μM.

후처리

  1. customThe reaction solvent was removed under reduced pressure
  2. customthe crude product was purified by reverse-phase preparative HPLC
  3. customC18 OBD (100×19 mm, 5 μm) column, 0.1% TFA in MeOH/H2O, gradient (65% to 95% over 4.5 min)

출처 및 근거

ORD 기록
ord-2ac308ec879c48ca8e2e4506ada6fed8
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431563B2

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