2,6-Lutidine → 2(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-methanesulfonylmethyl-1H-pyrazol-3-yl)-propionamide

HRID 546016

반응식

HRID 546016 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH3:21])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.N1C(C)=CC=CC=1C.[CH3:42][S:43](CN1C=CC(N)=N1)(=[O:45])=[O:44]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:22][CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][S:43]([CH3:42])(=[O:45])=[O:44])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

참가 물질

6

반응물 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 671889131-methanesulfonylmethyl-1H-pyrazol-3-ylamineHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazole

생성물 1

HCID 671902042(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-methanesulfonylmethyl-1H-pyrazol-3-yl)-propionamide수율 90.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
25 °C

실험 절차

To a solution containing 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in PCT WO 2004/052869 A1, Example 1, 100 mg, 0.30 mmol) in methylene chloride (20 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (166 μL, 0.33 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (46 μL, 0.39 mmol) was added to the solution at 0° C. After 1 h, 1-methanesulfonylmethyl-1H-pyrazol-3-ylamine (0.30 mmol based on theory) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with 1.0 M aqueous hydrochloric acid solution, dried over sodium sulfate, concentrated in vacuo and purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride) to afford 2(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-methanesulfonylmethyl-1H-pyrazol-3-yl)-propionamide (133 mg, 90%) as a white solid: ESI-LRMS m/e calcd for C20H26ClN3O5S2 [M+] 487.1, found 488.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.22 (m, 2H, CH2), 1.43-1.94 (m, 8H, 4×CH2), 2.09-2.29 (m, 1H, CH), 2.86 (s, 3H, SO2CH3), 3.27 (s, 3H, SO2CH3), 3.58 (t, J=7.5 Hz, 1H, CH), 5.25 (s, 2H, NCH2), 6.87 (d, J=2.5 Hz, 1H, Ar), 7.48 (dd, Jo=8.1, Jm=1.6 Hz. 1H, Ar), 7.54 (d, J=2.5 Hz, 1H, Ar), 7.61 (d, Jm=1.6 Hz, 1H, Ar), 8.01 (d, Jo=8.1 Hz, 1H, Ar), 8.10 (brs, 1H, NH).

후처리

  1. waitAfter 1 h
  2. waitto proceed for 16 h
  3. washThe reaction solution was washed with 1.0 M aqueous hydrochloric acid solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 10 g; 0% methanol/methylene chloride to 10% methanol/methylene chloride)

출처 및 근거

ORD 기록
ord-dcc21db85bf44e9cb469f3a50585ffbe
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935699B2

연결된 노트

불러오는 중…