Hydrochloric Acid → N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(adamantan-1-ylmethoxy)-1-oxo-3-phenylpropan-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 879247ノート

反応式

HRID 879247 の反応式
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]12[CH2:55][CH:50]3[CH2:51][CH:52]([CH2:54][CH:48]([CH2:49]3)[CH2:47]1)[CH2:53]2)=[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]12[CH2:47][CH:48]3[CH2:54][CH:52]([CH2:51][CH:50]([CH2:49]3)[CH2:55]1)[CH2:53]2)=[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]

参加物

5

反応物 4

HCID 313Hydrochloric Acid2 回HCID 5003444Sodium cyanoborohydride2 回HCID 10529182(3R,4S,5S)-tert-butyl 4-((S)-2-(((benzyloxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoateHCID 86698263N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(adamantane-1-ylmethoxy)-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 sodium trifluoro acetate2 回

生成物 1

HCID 56952077N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(adamantan-1-ylmethoxy)-1-oxo-3-phenylpropan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

反応条件

温度
100 °C

実験手順

26 mg (26 μmol) of N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(adamantane-1-ylmethoxy)-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 sodium trifluoroacetate (intermediate 29) and 33.9 μl of 15% aqueous amber aldehyde acid solution (53 μmol) were dissolved in 957 μl of a 1:1-dioxane/water composition and heated for 1 hour at a temperature of 100° C. After a short cooling period 1.81 mg (29 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 18.5 mg (73% o. th.) of the title compound.

後処理

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

出典と根拠

ORDレコード
ord-a012155d902340d7b2a4fcd0f1c9f9ee
出典データセット
uspto-grants-2015_03
特許番号
US08987209B2

反応ノート

読み込み中…