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Dichloromethane → 2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-2-methyl-3-thioxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide, hydrochloride salt

HRID 74741
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인쇄 미리보기

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HRID 74741 반응식
C1C2C(COC([NH:18][C:19]([CH3:68])([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:64]([CH3:67])[CH2:65][CH3:66])[C@H:33]([O:62][CH3:63])[CH2:34][C:35]([N:37]3[CH2:41][CH2:40][CH2:39][C@H:38]3[C@H:42]([O:60][CH3:61])[C@@H:43]([CH3:59])[C:44]([NH:46][C@@H:47]([CH2:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=3)[C:48]([O:50][CH3:51])=[O:49])=[S:45])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH3:20])=O)C3C(=CC=CC=3)C=2C=CC=1.C(NCC)C.[Cl:74]CCl>>[ClH:74].[CH3:20][C:19]([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:64]([CH3:67])[CH2:65][CH3:66])[C@H:33]([O:62][CH3:63])[CH2:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C@H:42]([O:60][CH3:61])[C@@H:43]([CH3:59])[C:44]([NH:46][C@@H:47]([CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:48]([O:50][CH3:51])=[O:49])=[S:45])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])([CH3:68])[NH2:18]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

4

반응물 3

HCID 6344DichloromethaneHCID 8021DiethylamineHCID 89573045N-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-2-methyl-3-thioxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

생성물 1

HCID 131731849
2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-2-methyl-3-thioxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide, hydrochloride salt
수율 70%

실험 절차

According to general procedure A, from #43 (176 mg, 0.184 mmol, 1 eq.), dichloromethane (4 mL, 0.05 M) and diethylamine (4 mL) was synthesized the crude desired material, which was purified by reverse phase chromatography (Method C). The resulting trifluoroacetic acid salt was dissolved in methanol, treated with a 4 M solution of hydrochloric acid in dioxane, and concentrated in vacuo to give #45 (100 mg, 70%) as a white solid. LC-MS: m/z 734.6 [M+H+], retention time=0.72 minutes; 1H NMR (400 MHz, CD3OD), presumed to be a mixture of rotamers, characteristic signals: δ 7.18-7.31 (m, 5H), 5.41-5.47 and 5.55-5.62 (2 m, total 1H), 3.73 and 3.76 (2 s, total 3H), 3.35 and 3.36 (2 s, total 3H), 3.10 and 3.15 (2 br s, total 3H), 1.62 and 1.64 (2 s, total 3H), 1.53 and 1.55 (2 s, total 3H), [1.25 (d, J=6.6 Hz) and 1.29 (d, J=6.5 Hz), total 3H], 0.84-0.91 (m, 3H).

후처리

  1. customwas purified by reverse phase chromatography (Method C)
  2. dissolutionThe resulting trifluoroacetic acid salt was dissolved in methanol
  3. additiontreated with a 4 M solution of hydrochloric acid in dioxane
  4. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-0be0d8bc949644579e4061688245c590
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08828401B2

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