1-Hydroxybenzotriazole → N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycabonylglycylamino)-L-Proline 4-Phenylbenzylamide

HRID 2185454노트

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HRID 2185454 반응식
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.FC(F)(F)C(O)=O.[C:30]1([C:36]2[CH:43]=[CH:42][C:39]([CH2:40][NH2:41])=[CH:38][CH:37]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[C:44]([O:48][C:49]([NH:51][CH2:52][C:53]([NH:55][C@H:56]1[CH2:60][N:59]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C@H:58]([C:68](O)=[O:69])[CH2:57]1)=[O:54])=[O:50])([CH3:47])([CH3:46])[CH3:45]>ClCCl.C(N(CC)CC)C>[C:30]1([C:36]2[CH:37]=[CH:38][C:39]([CH2:40][NH:41][C:68](=[O:69])[C@@H:58]3[CH2:57][C@@H:56]([NH:55][C:53](=[O:54])[CH2:52][NH:51][C:49]([O:48][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:50])[CH2:60][N:59]3[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[CH:42][CH:43]=2)[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

참가 물질

7

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341559trans-4-(N-tert-butoxycarbonylglycyl)amino-N-tert-butoxycarbonyl-L-prolineHCID 224587204-Phenylbenzylamine trifluoroacetate

생성물 1

HCID 131723254N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycabonylglycylamino)-L-Proline 4-Phenylbenzylamide수율 83.2%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

실험 절차

Triethylamine (130 μL), 1-hydroxybenzotriazole (59 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (89 mg) were added to a solution of the 4-phenylbenzylamine trifluoroacetate (B, 126 mg) and trans-4-(N-tert-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-proline (Compound D103 (B), 150 mg) in dichloromethane (10 mL) at 0° C. The mixture was stirred at room temperature for 16 hr and concentrated in vacuo. The residue was diluted with ethyl acetate and washed with 1 N hydrochloric acid, water, saturated sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (chloroform then chloroform:methanol=99:1 to 98:2, v/v) to give the title compound (178 mg) as a colorless foam:1H NMR (400 MHz, CDCl3) δ 1.45 (s, 18H), 1,67 (s, 2H), 2.01 (brs, 1H), 2.64 (br s, 1H), 3.27 (br s, 1H), 3.68-3.81 (m, 3H), 4.23-4.70 (m, 3H), 5.17 (br s, 1H), 6.43 (br s, 1H), 7.32-7.36 (m, 3H), 7.44 (t, J=7.6 Hz, 2H), and 7.53-7.57 (m, 4H).

후처리

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with 1 N hydrochloric acid, water, saturated sodium hydrogen carbonate, and brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (chloroform

출처 및 근거

ORD 기록
ord-156795b7c15948808f2181f6e80bc2d2
출처 데이터셋
uspto-grants-2002_06
특허 번호
US06399629B1

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