Trityl chloride → Trt-Phe-Gly

HRID 251513

반응식

HRID 251513 반응식
[CH:1]1[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]([NH2:16])[C:9]([NH:11][CH2:12][C:13]([OH:15])=[O:14])=[O:10])=[CH:5][CH:6]=1.[C:17](Cl)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O.CC(O)C.C(NCC)C>[NH:16]([C:17]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C@H:8]([C:9]([NH:11][CH2:12][C:13]([OH:15])=[O:14])=[O:10])[CH2:7][C:4]1[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=1

참가 물질

6

반응물 2

HCID 6456Trityl chlorideHCID 6992304Phe-Gly

생성물 1

HCID 101008440Trt-Phe-Gly수율 64.6%

시약·촉매·용매 3

HCID 962Water용매2회HCID 3776Isopropanol용매HCID 8021Diethylamine용매

실험 절차

1.1 g (5 mmol) of Phe-Gly (manufactured and sold by PEPTIDE INSTITUTE INC., Japan) was dissolved in a mixture of 2 ml of water, 2 ml of 2-propanol and 1.5 ml of diethylamine to obtain a solution. To the obtained solution was gradually added 1.8 g (6.5 mmol) of trityl chloride, followed by stirring for one hour. To the resultant reaction mixture was added water, to thereby generate a precipitate. The generated precipitate was collected, washed with water and then dissolved in 5 ml of acetic acid, to thereby obtain an acidic solution. The solvents were distilled off from the obtained acidic solution under reduced pressure, to thereby obtain 1.5 g of Trt-Phe-Gly. 604 mg (1.3 mmol) of the obtained Trt-Phe-Gly, 158 mg (1.3 mmol) of DMAP and 853 mg (1.0 mmol) of paclitaxel were dissolved in 20 ml of methylene chloride to obtain a solution. To the obtained solution was added 164 mg (1.3 mmol) of DIPC and stirred overnight at room temperature to effect a reaction. After completion of the reaction, the solvents were distilled off from the resultant reaction mixture under reduced pressure. The resultant residue was purified by silica gel column chromatography (silica gel: Art No. 9385, Silica gel 60, 200-400 mesh, manufactured and sold by Merck KGaA, Germany; column: 4.0×30 cm; eluent: methylene chloride/acetonitrile ratio=80/20), to thereby obtain 980 mg of 2′-Trt-Phe-Gly-paclitaxel. 800 mg of the obtained 2′-Trt-Phe-Gly-paclitaxel was treated with 10 ml of 90% acetic acid to effect a reaction for removing an N-trityl group. The resultant product was purified by silica gel column chromatography (silica gel Art No. 9385, Silica gel 60, 200-400 mesh, manufactured and sold by Merck KGaA, Germany; column 4.0×30 cm; eluent: methylene chloride/methanol/acetonitrile ratio=95/5/5), and subsequently converted from an acetate to a corresponding hydrochloride with an ion exchange resin, to thereby obtain 450 mg of 2′-Phe-Gly-paclitaxel hydrochloride (186).

후처리

  1. customto obtain a solution
  2. customTo the resultant reaction mixture
  3. customThe generated precipitate was collected
  4. washwashed with water
  5. dissolutiondissolved in 5 ml of acetic acid
  6. customto thereby obtain an acidic solution
  7. distillationThe solvents were distilled off from the obtained acidic solution under reduced pressure

출처 및 근거

ORD 기록
ord-799cf979c7c64d76bf075a0d95b18e23
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07863408B2

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