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 879248Notes

Reaction equation

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:63]([CH3:66])[CH2:64][CH3:65])[C@H:27]([O:61][CH3:62])[CH2:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C@H:36]([O:59][CH3:60])[C@@H:37]([CH3:58])[C:38]([NH:40][C@@H:41]([CH2:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1)[CH2:42][O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[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:76][C:77](=[O:106])[CH2:78][C@@H:79](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:77]([CH2:78][CH2:79][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:63]([CH3:66])[CH2:64][CH3:65])[C@H:27]([O:61][CH3:62])[CH2:28][C:29]([N:31]1[CH2:35][CH2:34][CH2:33][C@H:32]1[C@H:36]([O:59][CH3:60])[C@@H:37]([CH3:58])[C:38]([NH:40][C@@H:41]([CH2:51][C:52]1[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=1)[CH2:42][O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:39])=[O:30])[CH3:25])=[O:23])[CH:19]([CH3:20])[CH3:21])=[O:16])[CH:12]([CH3:14])[CH3:13])([OH:106])=[O:76]

Participants

Reactant 4

HCID 313Hydrochloric Acid2×

HCID 5003444Sodium cyanoborohydride2×

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

HCID 86698264N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-(benzyloxy)-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 trifluoroacetate2×

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

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-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 33) and 33.7 μl of 15% aqueous amber aldehyde acid solution (52 μmol) were dissolved in 953 μl of a 1:1-dioxane/water composition and heated for 1 hour at a temperature of 100° C. After a short cooling period 1.80 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 15.2 mg (65% o. th.) of the title compound.

Workup

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

Sources & evidence

ORD record: ord-a479328c152b40b5bad2446f7f718486
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987209B2

Reaction notes

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