2,6-Lutidine → 3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid tert-butyl ester

HRID 545998

反応式

HRID 545998 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.N1C(C)=CC=CC=1C.[C:42]([O:46][C:47](=[O:56])[CH:48](N1C=CC(N)=N1)C)([CH3:45])([CH3:44])[CH3:43]>C(Cl)Cl>[C:42]([O:46][C:47](=[O:56])[CH2:48][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)([CH3:45])([CH3:44])[CH3:43]

参加物

6

反応物 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 671896933-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-1-methyl-pyrazoleHCID 67190546(3-Amino-pyrazol-1-yl)-propionic acid tert-butyl ester

生成物 1

HCID 671898343-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid tert-butyl ester収率 73%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

反応条件

温度
0 °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, 2.66 g, 8.04 mmol) in methylene chloride (20 mL), a 2.0 M solution of oxalylchloride in methylene chloride (4.42 mL, 8.84 mmol) was added and allowed to stir for 1 h at 0° C. then for 1 h at 25° C. 2,6-lutidine (1.12 g, 10.0 mmol) was then added dropwise at 0° C., turning the solution light brown and resulting in effervescence. To this solution was added (3-amino-pyrazol-1-yl)-propionic acid tert-butyl ester (1.87 g, 8.84 mmol) dissolved in methylene chloride (5 mL). The reaction was allowed to proceed at 0° C. for 1 h and then overnight at 25° C. The reaction was washed with 1.0 M aqueous hydrochloric acid solution (20 mL) and the organic layer was dried with anhydrous sodium sulfate. The solvent was then removed in vacuo and was purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 10% ethyl acetate/methylene chloride) to afford 3-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid tert-butyl ester (3.06 g, 73%) as a white solid: ESI-LRMS m/e calcd for C25H34ClN3O5S [M+] 523.2, found 524.4 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.03-1.20 (m, 2H, CH2), 1.40 (s, 9H, 3×CH3), 1.39-1.92 (m, 8H, 4×CH2), 2.10-2.31 (m, 1H, CH), 2.70 (t, J=6.6 Hz, 2H, COCH2), 3.25 (s, 3H, SO2CH3), 3.57 (t, J=7.6 Hz, 1H, CH), 4.21 (t, J=6.6 Hz, 2H, NCH2), 6.60 (d, J=2.3 Hz, 1H, Ar), 7.28 (d, J=2.3 Hz, 1H, Ar), 7.45 (dd, Jo=8.2, Jm=1.7 Hz. 1H, Ar), 7.58 (d, Jm=1.7 Hz, 1H, Ar), 8.06 (d, Jo=8.2 Hz, 1H, Ar), 8.17 (s, 1H, NH).

後処理

  1. waitfor 1 h at 25° C
  2. customresulting in effervescence
  3. waitto proceed at 0° C. for 1 h
  4. customovernight
  5. customat 25° C
  6. washThe reaction was washed with 1.0 M aqueous hydrochloric acid solution (20 mL)
  7. dry with materialthe organic layer was dried with anhydrous sodium sulfate
  8. customThe solvent was then removed in vacuo
  9. customwas purified by ISCO flash column chromatography (Teledyne Isco RediSep Flash Column 120 g; 10% ethyl acetate/methylene chloride)

出典と根拠

ORDレコード
ord-e4a5c9211d1646e59f9b7e9e337f4f62
出典データセット
uspto-grants-2011_05
特許番号
US07935699B2

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