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 879250노트

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HRID 879250 반응식
[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]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 7504BenzylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 71111548t-Boc-N-MMAF2회

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-429820342db5437db74c0dc8eed142c1
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987209B2

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