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Triethylamine → N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methyl-L-valyl-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

HRID 2282824
ノート
印刷プレビュー

反応式

HRID 2282824 の反応式
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]([CH3:46])[C@H:19]([C:23]([NH:25][C@H:26]([C:30]([N:32]([C@@H:34]([C@@H:42]([CH3:45])[CH2:43][CH3:44])[C@H:35]([O:40][CH3:41])[CH2:36][C:37](O)=[O:38])[CH3:33])=[O:31])[CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.[CH3:48][O:49][C@@H:50]([C@@H:68]1[CH2:72][CH2:71][CH2:70][NH:69]1)[C@@H:51]([CH3:67])[C:52]([NH:54][C@H:55]([C:63]([O:65][CH3:66])=[O:64])[CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)=[S:53].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C)C=O.ClCCl>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([N:18]([CH3:46])[C@H:19]([C:23]([NH:25][C@H:26]([C:30]([N:32]([C@@H:34]([C@@H:42]([CH3:45])[CH2:43][CH3:44])[C@H:35]([O:40][CH3:41])[CH2:36][C:37]([N:69]3[CH2:70][CH2:71][CH2:72][C@H:68]3[C@H:50]([O:49][CH3:48])[C@@H:51]([CH3:67])[C:52]([NH:54][C@@H:55]([CH2:56][C:57]3[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=3)[C:63]([O:65][CH3:66])=[O:64])=[S:53])=[O:38])[CH3:33])=[O:31])[CH:27]([CH3:29])[CH3:28])=[O:24])[CH:20]([CH3:22])[CH3:21])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 60042710(5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oic acidHCID 131731848methyl N-{(2R,3R)-3-methoxy-2-methyl-3-[(2S)-pyrrolidin-2-yl]propanethioyl}-L-phenylalaninate, hydrochloride salt

生成物

1
HCID 89582401N-[(9H-fluoren-9-ylmethoxy)carbonyl]-N-methyl-L-valyl-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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

According to general procedure D, from #8 (247 mg, 0.387 mmol, 1 eq.), #39 (186 mg, ≦0.450 mmol, 1.2 eq.), dichloromethane (10 mL, 0.04 M), N,N-dimethylformamide (2 mL), HATU (176 mg, 0.464 mmol, 1.2 eq.) and triethylamine (189 mL, 1.35 mmol, 3.5 eq.) was synthesized the crude desired material, which was purified by silica gel chromatography (Gradient: 0% to 25% acetone in heptane) to give #40 (410 mg, 90% over 2 steps) as an off-white solid. LC-MS: m/z 984.7 [M+H+], 1006.7 [M+Na+], retention time=1.15 minutes; HPLC (Protocol C): retention time=9.683 minutes (purity >99%); 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [10.19 (br d, J=7 Hz) and 10.49 (br d, J=8 Hz), total 1H], 7.90 (d, J=7.5 Hz, 2H), 7.60-7.65 (m, 2H), 7.38-7.45 (m, 2H), 7.29-7.35 (m, 2H), 7.14-7.28 (m, 5H), [5.20 (ddd, J=11, 7, 4 Hz) and 5.35-5.43 (m), total 1H], 3.65 and 3.69 (2 s, total 3H), [1.15 (d, J=6.5 Hz) and 1.18 (d, J=6.4 Hz), total 3H].

後処理

  1. customwas purified by silica gel chromatography (Gradient: 0% to 25% acetone in heptane)
  2. customto give #40 (410 mg, 90% over 2 steps) as an off-white solid
  3. additiona mixture of rotamers, characteristic signals

出典と根拠

ORDレコード
ord-5da6678a0e134b1184947afade585401
出典データセット
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09138486B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート