1,2-Dichloroethane → N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzylamino)-1-oxo-3-phenylpropane-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 879250ノート

反応式

HRID 879250 の反応式
[C:1]([O:5][C:6]([N:8]([CH3:59])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:55]([CH3:58])[CH2:56][CH3:57])[C@H:25]([O:53][CH3:54])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:51][CH3:52])[C@@H:35]([CH3:50])[C:36]([NH:38][C@H:39]([C:47](O)=[O:48])[CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:37])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:60]([NH2:67])[C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1.C(N(CC)C(C)C)(C)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH3:59])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:55]([CH3:58])[CH2:56][CH3:57])[C@H:25]([O:53][CH3:54])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:51][CH3:52])[C@@H:35]([CH3:50])[C:36]([NH:38][C@@H:39]([CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:47]([NH:67][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)=[O:48])=[O:37])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:18])[CH3:19])=[O:14])[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:2])([CH3:4])[CH3:3]

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 7504BenzylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 71111548t-Boc-N-MMAF2 回

生成物 1

HCID 89428507N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzylamino)-1-oxo-3-phenylpropane-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

36 mg (43 μmol) of N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(1S)-1-carboxy-2-phenylethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (intermediate 39) and 4.6 mg (43 μmol) of benzyl amine were absorbed in 5 ml of DMF, mixed with 7.5 μl (88 μmol) of N,N-diisopropylethylamine, 10 mg (65 μmol) of HOBt as well as 10 mg (52 μmol) of EDC, and then stirred over night at RT. Then, the reaction composition was evaporated and the residue purified by means of preparative HPLC. This way, 29 mg (73% o. th.) of Fmoc protected intermediate of N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzylamino)-1-oxo-3-phenylpropane-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide were obtained.

後処理

  1. customThen, the reaction composition was evaporated
  2. customthe residue purified by means of preparative HPLC

出典と根拠

ORDレコード
ord-429820342db5437db74c0dc8eed142c1
出典データセット
uspto-grants-2015_03
特許番号
US08987209B2

反応ノート

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