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

HRID 545993

反応式

HRID 545993 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:25][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:22](O)=[O:23])[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.[N:37]1[C:42](C)=CC=C[C:38]=1C.Cl.CNC>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:25][CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30]2)[C:13]([NH:15][C:16]2[CH:20]=[CH:19][N:18]([CH2:21][C:22](=[O:23])[N:37]([CH3:42])[CH3:38])[N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

参加物

6

反応物 4

HCID 79372,6-LutidineHCID 10473Dimethylamine, hydrochlorideHCID 65578Oxalyl chlorideHCID 67189335{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-acetic acid

生成物 1

HCID 671906552(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(1-dimethylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamide収率 60.5%

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 {3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-acetic acid (prepared in example 3, 100 mg, 0.22 mmol) in methylene chloride (2 mL), was then added a 2.0 M solution of oxalylchloride in methylene chloride (121 μL, 0.24 mmol) at 0° C. and allowed to stir at 25° C. for 1 h, after which time 2,6-lutidine (28 μL, 0.24 mmol) was added to the solution. After 1 h, dimethylamine hydrochloride (20 mg, 0.24 mmol) was added and the reaction was allowed to proceed for 16 h. The reaction solution was washed with saturated aqueous ammonium chloride solution, the organic phase was 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-dimethylcarbamoylmethyl-1H-pyrazol-3-yl)-propionamide (64 mg, 60%) as a white solid: ESI-LRMS m/e calcd for C22H29ClN4O4S [M+] 480.2, found 481.3 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.02-1.22 (m, 2H, CH2), 1.41-1.93 (m, 8H, 4×CH2), 2.18-2.27 (m, 1H, CH), 2.97 (s, 3H, NCH3), 3.03 (s, 3H, NCH3), 3.26 (s, 3H, SO2CH3), 3.54 (t, J=7.5 Hz, 1H, CH), 4.81 (s, 2H, NCH2), 6.71 (d, J=2.3 Hz, 1H, Ar), 7.34 (d, J=2.3 Hz, 1H, Ar), 7.43 (dd, Jo=8.2, Jm=1.8 Hz, 1H, Ar), 7.57 (d, Jm=1.8 Hz, 1H, Ar), 7.96 (s, 1H, NH), 8.06 (d, Jo=8.2 Hz, 1H, Ar).

後処理

  1. waitAfter 1 h
  2. waitto proceed for 16 h
  3. washThe reaction solution was washed with saturated aqueous ammonium chloride solution
  4. concentrationthe organic phase was concentrated in vacuo
  5. 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-c6c1c3c55bcf495aaf8cee10112937b7
出典データセット
uspto-grants-2011_05
特許番号
US07935699B2

関連ノート

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