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Hydrochloric Acid → N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

HRID 879246
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인쇄 미리보기

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HRID 879246 반응식
F[C:2](F)(F)C([O-])=O.[Na+].[CH3:9][NH:10][C@H:11]([C:15]([NH:17][C@H:18]([C:22]([N:24]([C@@H:26]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:27]([O:66][CH3:67])[CH2:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C@H:36]([O:64][CH3:65])[C@@H:37]([CH3:63])[C:38]([NH:40][C@@H:41]([CH2:56][C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:42]([O:44][CH2:45][C:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=[CH:48][CH:47]=1)=[O:43])=[O:39])=[O:30])[CH3:25])=[O:23])[CH:19]([CH3:21])[CH3:20])=[O:16])[CH:12]([CH3:14])[CH3:13].C([BH3-])#N.[Na+].Cl.C([O:81][C:82](=[O:111])[CH2:83][C@@H:84](OC)[C@@H](N(C(=O)[C@H](C(C)C)NC(OCC1C=CC=CC=1)=O)C)[C@@H](C)CC)(C)(C)C>>[C:82]([CH2:83][CH2:84][CH2:9][N:10]([CH3:2])[C@H:11]([C:15]([NH:17][C@H:18]([C:22]([N:24]([C@@H:26]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:27]([O:66][CH3:67])[CH2:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C@H:36]([O:64][CH3:65])[C@@H:37]([CH3:63])[C:38]([NH:40][C@@H:41]([CH2:56][C:57]1[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=1)[C:42]([O:44][CH2:45][C:46]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:49]=[CH:48][CH:47]=1)=[O:43])=[O:39])=[O:30])[CH3:25])=[O:23])[CH:19]([CH3:20])[CH3:21])=[O:16])[CH:12]([CH3:14])[CH3:13])([OH:111])=[O:81]
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5

반응물 4

HCID 313Hydrochloric Acid2회HCID 5003444Sodium cyanoborohydride2회HCID 10529182(3R,4S,5S)-tert-butyl 4-((S)-2-(((benzyloxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoateHCID 86698261N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide sodium trifluoroacetate
2회

생성물 1

HCID 56953551N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

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온도
100 °C

실험 절차

24 mg (24 μmol) of N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1-naphthylmethoxy)-1-oxo-3-phenylpropane-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide sodium trifluoroacetate (intermediate 21) and 31.5 μl of 15% aqueous amber aldehyde acid solution (49 μmol) were dissolved in 900 μl of a 1:1-dioxane/water composition and heated for 1 hour at a temperature of 100° C. After a short cooling period 1.7 mg (27 μmol) of sodium cyanoborohydride were added. The reaction composition was formulated with 0.1 of N hydrochloric acid to pH 3 and heated for 2 hours at a temperature of 100° C. It was reheated again for 2 hours at 100° C. after the same amounts of amber aldehyde acid solution, sodium cyanoborohydride, and hydrochloric acid had been added once again. Afterwards, the reaction composition had been separated directly by means of preparative HPLC. The yield was 20.1 mg (86% o. th.) of the title compound.

후처리

  1. additionwere added
  2. customAfterwards, the reaction composition had been separated directly by means of preparative HPLC

출처 및 근거

ORD 기록
ord-76236c85a8064b6fadcc444c5bf4e16d
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08987209B2

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