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

HRID 2185454ノート

反応式

HRID 2185454 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-156795b7c15948808f2181f6e80bc2d2
出典データセット
uspto-grants-2002_06
特許番号
US06399629B1

反応ノート

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