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

HRID 882598Notes

Reaction equation

F[C:2](F)(F)[C:3]([OH:5])=[O:4].[CH3:8][NH:9][C@H:10]([C:14]([NH:16][C@H:17]([C:21]([N:23]([C@@H:25]([C@@H:61]([CH3:64])[CH2:62][CH3:63])[C@H:26]([O:59][CH3:60])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:57][CH3:58])[C@@H:36]([CH3:56])[C:37]([NH:39][C@@H:40]([CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:41](N1CCCCO1)=[O:42])=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH:11]([CH3:13])[CH3:12].C1C2C([CH2:78][O:79]C(N(C)[C@H](C(N[C@H](C(N([C@@H]([C@@H](C)CC)[C@H](OC)CC(O)=O)C)=O)C(C)C)=O)C(C)C)=O)C3C(=CC=CC=3)C=2C=CC=1.O=[CH:112][CH2:113]CC(O)=O.C([BH3-])#N.[Na+]>>[C:3]([CH2:2][CH2:112][CH2:113][N:9]([CH3:8])[C@H:10]([C:14]([NH:16][C@H:17]([C:21]([N:23]([C@@H:25]([C@@H:61]([CH3:64])[CH2:62][CH3:63])[C@H:26]([O:59][CH3:60])[CH2:27][C:28]([N:30]1[CH2:34][CH2:33][CH2:32][C@H:31]1[C@H:35]([O:57][CH3:58])[C@@H:36]([CH3:56])[C:37]([NH:39][C@@H:40]([CH2:49][C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1)[C:41]([O:79][CH3:78])=[O:42])=[O:38])=[O:29])[CH3:24])=[O:22])[CH:18]([CH3:20])[CH3:19])=[O:15])[CH:11]([CH3:13])[CH3:12])([OH:5])=[O:4]

Participants

Reactant 4

HCID 11124-Oxobutanoic acid

HCID 5003444Sodium cyanoborohydride

HCID 54764105N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-{[(2S)-1-(1,2-oxazinan-2-yl)-1-oxo-3-phenylpropan-2-yl]amino}-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide trifluoroacetate

HCID 60042710(5S,8S,11S,12R)-11-((S)-sec-butyl)-1-(9H-fluoren-9-yl)-5,8-diisopropyl-12-methoxy-4,10-dimethyl-3,6,9-trioxo-2-oxa-4,7,10-triazatetradecan-14-oic acid

Product 1

HCID 56952186N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-2-methyl-3-oxopropyl]pyrrolidin-1-yl)-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Procedure

First, in analogy to the synthesis described in Intermediate 14, proceeding from Intermediates 4 and 39, the amine compound N-methyl-L-valyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-3-{[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino}-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide was prepared. 7 mg (0.009 mmol) of this compound were then used, in analogy to the preparation of Intermediate 61, by reaction with 4-oxobutanoic acid in the presence of sodium cyanoborohydride, to obtain 2 mg (22% of theory) of the title compound in the form of a colourless foam.

Sources & evidence

ORD record: ord-4ff05ae036fc45cfa1d1b8d9ef4d99e7
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08992932B2

Reaction notes

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