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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
ノート
印刷プレビュー

反応式

HRID 74741 の反応式
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]
参加物実験手順後処理出典と根拠反応ノート

参加物

4

反応物 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

生成物 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
収率 70%

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-0be0d8bc949644579e4061688245c590
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08828401B2

反応ノート

読み込み中…

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