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

HRID 546096노트

반응식

HRID 546096 반응식
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

참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 67190452HCID 67190452, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
25 °C

실험 절차

(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).

후처리

  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

출처 및 근거

ORD 기록
ord-0329cd75cdd84679a6a28d1091d42254
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935699B2

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