Hydrochloric Acid → N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzyloxy)-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 882597Notes

Reaction equation

HRID 882597 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:62]([CH3:65])[CH2:63][CH3:64])[C@H:26]([O:60][CH3:61])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:58][CH3:59])[C@@H:36]([CH3:57])[C:37]([NH:39][C@@H:40]([CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:41][O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH:11]([CH3:13])[CH3:12].[C:66]([OH:72])(=[O:71])[CH2:67][CH2:68][CH:69]=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:66]([CH2:67][CH2:68][CH2:69][N:9]([CH3:8])[C@H:10]([C:14]([NH:16][C@H:17]([C:21]([N:23]([C@@H:25]([C@@H:62]([CH3:65])[CH2:63][CH3:64])[C@H:26]([O:60][CH3:61])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:58][CH3:59])[C@@H:36]([CH3:57])[C:37]([NH:39][C@@H:40]([CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:41][O:42][CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH:11]([CH3:13])[CH3:12])([OH:72])=[O:71]

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 11124-Oxobutanoic acid2×HCID 5003444Sodium cyanoborohydride2×HCID 86678345N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzyloxy)-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

Product 1

HCID 56952078N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzyloxy)-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

24 mg (26 μmol) of N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzyloxy)-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 33.7 μl of a 15% aqueous succinaldehydic acid solution (52 μmol) were dissolved in 953 μl of a 1:1-dioxane/water mixture and heated to 100° C. for 1 h. After brief cooling, 1.80 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. 15.2 mg (65% 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-5d3fe705501b462fbcfbb1aa2018836a
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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