Trifluoroacetic acid → N-[1-(3-amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 546096ノート

反応式

HRID 546096 の反応式
C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][N:15]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:40])[C@@H:22]([C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[C:31]([Cl:39])[CH:30]=3)[CH2:23][CH:24]3[CH2:28][CH2:27][CH2:26][CH2:25]3)=[N:16]2)[CH:9]=1)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][C:8]1[CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=1)[CH2:14][N:15]1[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:40])[C@@H:22]([C:29]2[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[C:31]([Cl:39])[CH:30]=2)[CH2:23][CH:24]2[CH2:28][CH2:27][CH2:26][CH2:25]2)=[N:16]1

参加物

4

反応物 2

HCID 6422Trifluoroacetic acidHCID 67190452HCID 67190452、化合物

生成物 1

HCID 67190250N-[1-(3-amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide収率 83.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

(3-{3-[2-(R)-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-ylmethyl}-phenyl)-carbamic acid tert-butyl ester (prepared in Example 57, 501 mg, 0.83 mmol) was dissolved in methylene chloride (5 mL) and trifluoroacetic acid (500 μL) was added. The reaction stirred at 25° C. for 3 h. The reaction was concentrated in vacuo to half the reaction volume, diluted with toluene and concentrated in vacuo to dryness. The reaction was dissolved in ethyl acetate (25 mL), washed with a saturated aqueous sodium bicarbonate solution (2×10 mL), saturated aqueous brine solution (10 mL), dried over magnesium sulfate and concentrated in vacuo to give the desired product, N-[1-(3-amino-benzyl)-1H-pyrazol-3-yl]-2-(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (348 mg, 83%) as an off white powder: ESI-LRMS m/e calcd for C25H29ClN4O3S [M+] 500.16, found 501.20 [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.06-1.21 (m, 2H, CH2), 1.41-1.92 (m, 8H, 4×CH2), 2.14-2.32 (m, 1H, CH), 3.25 (s, 3H, SO2CH3), 3.53-3.68 (m, 1H, CH), 5.02 (s, 2H, NCH2), 6.45-6.55 (m, 1H, Ar), 6.56-0.665 (m, 2H, Ar), 6.68 (s, 1H, Ar), 7.00-7.14 (m, 1 H, Ar), 7.32 (s, 1H, Ar), 7.45 (d, Jo=7.8 Hz. 1H, Ar), 7.60 (s, 1H, Ar), 7.75-8.23 (m, 2H, Ar and NH).

後処理

  1. concentrationThe reaction was concentrated in vacuo to half the reaction volume
  2. additiondiluted with toluene
  3. concentrationconcentrated in vacuo to dryness
  4. dissolutionThe reaction was dissolved in ethyl acetate (25 mL)
  5. washwashed with a saturated aqueous sodium bicarbonate solution (2×10 mL), saturated aqueous brine solution (10 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-0329cd75cdd84679a6a28d1091d42254
出典データセット
uspto-grants-2011_05
特許番号
US07935699B2

反応ノート

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