2,6-Lutidine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(4-methanesulfonyl-benzyl)-1H-pyrazol-3-yl]-propionamide

HRID 546013

반응식

HRID 546013 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]([C:46]1[CH:58]=[CH:57][C:49](CN2C=CC(N)=N2)=[CH:48][CH:47]=1)(=[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][C:49]3[CH:57]=[CH:58][C:46]([S:43]([CH3:42])(=[O:45])=[O:44])=[CH:47][CH:48]=3)[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 671887261-(4-methanesulfonyl-benzyl)1H-pyrazol-3-ylamineHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazole

생성물 1

HCID 248896662(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[1-(4-methanesulfonyl-benzyl)-1H-pyrazol-3-yl]-propionamide수율 88.6%

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-(4-methanesulfonyl-benzyl)-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-(4-methanesulfonyl-benzyl)-1H-pyrazol-3-yl]-propionamide (150 mg, 88%) as a white solid: ESI-LRMS m/e calcd for C26H30ClN3O5S2 [M+] 563.13, found 564.5 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.21 (m, 2H, CH2), 1.34-1.88 (m, 8H, 4×CH2), 2.09-2.29 (m, 1H, CH), 2.98 (s, 3 H, SO2CH3), 3.22 (s, 3H, SO2CH3), 3.56 (t, J=7.5 Hz, 1H, CH), 5.24 (AB, Jgem=15.9 Hz, 2H, NCH2), 6.76 (d, J=2.3 Hz, 1H, Ar), 7.14 (d, Jo=8.3 Hz, 2H, Ar), 7.38 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.44 (d, J=2.3 Hz, 1H, Ar), 7.53 (d, Jm=1.7 Hz, 1H, Ar), 7.75 (d, Jo=8.3 Hz, 2H, Ar), 7.91 (d, Jo=8.2 Hz, 1H, Ar), 8.34 (s, 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-99912905938747b89222984323d15857
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935699B2

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