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

HRID 546022

反応式

HRID 546022 の反応式
[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.N1[C:39](C)=[CH:38][CH:37]=[CH:36][C:35]=1[CH3:41].C(N1C=CC(N)=N1)C1C=CC=CC=1>C(Cl)Cl>[CH2:21]([N:18]1[CH:19]=[CH:20][C:16]([NH:15][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[C:2]([Cl:1])[CH:3]=2)[CH2:22][CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)=[N:17]1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:41]=1

参加物

6

反応物 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 15086161-benzyl-1H-pyrazol-3-amineHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazole

生成物 1

HCID 24889668N-(1-benzyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide収率 69.3%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
25 °C

実験手順

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 (181 μL, 0.36 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (70 μL, 0.61 mmol) was added to the solution at 0° C. After 1 h, crude 1-benzyl-1H-pyrazol-3-ylamine (0.42 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 N-(1-benzyl-1H-pyrazol-3-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (101 mg, 69%) as a white solid: ESI-LRMS m/e calcd for C25H28ClN3O3S [M+] 485.2, found 486.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.05-1.18 (m, 2H, CH2), 1.40-1.91 (m, 8H, 4×CH2), 2.10-2.31 (m, 1H, CH), 3.23 (s, 3H, SO2CH3), 3.56 (t, J=7.6 Hz, 1H, CH), 5.12 (s, 2H, NCH2), 6.69 (d, J=2.3 Hz, 1H, Ar), 7.12 (dd, Jo=7.2, Jm=1.7 Hz. 2H, Ar), 7.26-7.33 (m, 4H, Ar), 7.43 (dd, Jo=8.2, Jm=1.6 Hz. 1H, Ar), 7.57 (d, Jm=1.6 Hz, 1H, Ar), 8.04 (d, Jo=8.2 Hz. 1H, Ar), 8.27 (brs, 1H, NH).

後処理

  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)

出典と根拠

ORDレコード
ord-8266d1554e394f158624f92a11b04cb3
出典データセット
uspto-grants-2011_05
特許番号
US07935699B2

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