4-Oxobutanoic acid → N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S,3R)-1-(benzylamino)-3-hydroxy-1-oxobutan-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 879252Notes

Reaction equation

F[C:2](F)(F)[C:3]([O-:5])=[O:4].[Na+].C(O[C:14]([N:16]([CH3:56])[C@H:17]([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:52]([CH3:55])[CH2:53][CH3:54])[C@H:33]([O:50][CH3:51])[CH2:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C@H:42]([O:48][CH3:49])[C@H:43]([C:45]([OH:47])=O)[CH3:44])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH:18]([CH3:20])[CH3:19])=O)(C)(C)C.F[C:58](F)(F)[C:59]([O-:61])=O.[Na+].[CH2:65]([NH:72][C:73](=[O:79])[C@H:74]([C@@H](C)O)[NH2:75])[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1.N1(OC(N(C)C)=[N+](C)C)C2N=CC=C[C:83]=2N=N1.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O.O=CCCC(O)=O.C([BH3-])#N.[Na+]>>[C:3]([CH2:2][CH2:83][CH2:14][N:16]([CH3:56])[C@H:17]([C:21]([NH:23][C@H:24]([C:28]([N:30]([C@@H:32]([C@@H:52]([CH3:55])[CH2:53][CH3:54])[C@H:33]([O:50][CH3:51])[CH2:34][C:35]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C@H:42]([O:48][CH3:49])[C@@H:43]([CH3:44])[C:45]([NH:75][C@@H:74]([C@H:59]([OH:61])[CH3:58])[C:73]([NH:72][CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1)=[O:79])=[O:47])=[O:36])[CH3:31])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:22])[CH:18]([CH3:19])[CH3:20])([OH:5])=[O:4]

Participants

Reactant 6

HCID 11124-Oxobutanoic acid

HCID 6422Trifluoroacetic acid

HCID 5003444Sodium cyanoborohydride

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

HCID 86698265N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4 S,5S)-1-{(2S)-2-[(1R,2R)-2-carboxy-1-methoxypropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide sodium trifluoroacetate2×

HCID 86698266N-benzyl-L-threoninamide sodium trifluoroacetate

Product 1

HCID 56952798N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S,3R)-1-(benzylamino)-3-hydroxy-1-oxobutan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Procedure

First, the amine compound N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S,3R)-1-(benzylamino)-3-hydroxy-1-oxobutan-2-yl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide was produced as sodium trifluoroacetate, in analogy to the synthesis described in example 16 by means of coupling N-(tert.-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-2-carboxy-1-methoxypropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (intermediate 15) with N-benzyl-L-threoninamide sodium trifluoroacetate in the presence of O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate, followed by cleavage of the Boc protected group with the help of trifluoroacetic acid. Out of 21 mg (0.024 mmol) of this compound 20 mg (97% o. th.) of the title compound were obtained in analogy to the production of example 1, by means of treatment with 4-ketobutyric acid in the presence of sodium cyanoborohydride.

Sources & evidence

ORD record: ord-a427bdd3eaa94173914e7f55d8b808e7
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987209B2

Reaction notes

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