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 882596Notes

Reaction equation

HRID 882596 reaction equation
FC(F)(F)C(O)=O.[CH3:8][NH:9][C@H:10]([C:14]([NH:16][C@H:17]([C:21]([N:23]([C@@H:25]([C@@H:67]([CH3:70])[CH2:68][CH3:69])[C@H:26]([O:65][CH3:66])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:63][CH3:64])[C@@H:36]([CH3:62])[C:37]([NH:39][C@@H:40]([CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)[C:41]([O:43][CH2:44][C:45]12[CH2:54][CH:49]3[CH2:50][CH:51]([CH2:53][CH:47]([CH2:48]3)[CH2:46]1)[CH2:52]2)=[O:42])=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH:11]([CH3:13])[CH3:12].[C:71]([OH:77])(=[O:76])[CH2:72][CH2:73][CH:74]=O.C([BH3-])#N.[Na+].Cl>C(OC(N[C@H](C(N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(OC(C)(C)C)=O)=O)C(C)C)=O)C1C=CC=CC=1>[C:71]([CH2:72][CH2:73][CH2:74][N:9]([CH3:8])[C@H:10]([C:14]([NH:16][C@H:17]([C:21]([N:23]([C@@H:25]([C@@H:67]([CH3:70])[CH2:68][CH3:69])[C@H:26]([O:65][CH3:66])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:63][CH3:64])[C@@H:36]([CH3:62])[C:37]([NH:39][C@@H:40]([CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)[C:41]([O:43][CH2:44][C:45]12[CH2:46][CH:47]3[CH2:53][CH:51]([CH2:50][CH:49]([CH2:48]3)[CH2:54]1)[CH2:52]2)=[O:42])=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH:11]([CH3:13])[CH3:12])([OH:77])=[O:76]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 11124-Oxobutanoic acid2×HCID 5003444Sodium cyanoborohydride2×HCID 86678342N-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 trifluoro acetate

Product 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

Reagents, catalysts & solvents 1

HCID 10529182(3R,4S,5S)-tert-butyl 4-((S)-2-(((benzyloxy)carbonyl)amino)-N,3-dimethylbutanamido)-3-methoxy-5-methylheptanoateSolvent

Conditions

Temperature
100 °C

Procedure

26 mg (26 μmol) of 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 trifluoroacetate and 33.9 μl of a 15% aqueous succinaldehydic acid solution (53 μmol) were dissolved in 957 μl of a 1:1-dioxane/water mixture and heated to 100° C. for 1 h. After brief cooling, 1.81 mg (29 μmol) of sodium cyanoborohydride were added. The reaction mixture was adjusted to pH 3 by adding 0.1 N hydrochloric acid and the mixture was heated to 100° C. for a further 2 h. After again adding the same amounts of succinaldehydic acid solution, sodium cyanoborohydride and hydrochloric acid, the mixture was heated once again to 100° C. for 2 h. The reaction mixture was then separated directly into its components by means of preparative HPLC. 18.5 mg (73% of theory) of the title compound were thus obtained.

Workup

  1. temperaturethe mixture was heated once again to 100° C. for 2 h
  2. customThe reaction mixture was then separated directly into its components by means of preparative HPLC

Sources & evidence

ORD record
ord-8a05e7bf05a84a95a5d4a13a45be6cf9
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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