Trifluoroacetic acid → N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-amino-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 879249Notes

Reaction equation

HRID 879249 reaction equation
C(O[C:6]([N:8](C)[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:44]([CH3:47])[CH2:45][CH3:46])[C@H:25]([O:42][CH3:43])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:40][CH3:41])[C@H:35]([C:37](O)=[O:38])[CH3:36])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C.Cl.[NH2:50][C@H:51]([C:59]([NH2:61])=[O:60])[CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1.N1(OC(N(C)C)=[N+](C)C)[C:66]2N=CC=C[C:65]=2N=N1.F[P-](F)(F)(F)(F)F.F[C:87](F)(F)[C:88]([OH:90])=[O:89]>>[C:88]([CH2:87][CH2:65][CH2:66][N:8]([CH3:6])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:44]([CH3:47])[CH2:45][CH3:46])[C@H:25]([O:42][CH3:43])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:40][CH3:41])[C@@H:35]([CH3:36])[C:37]([NH:50][C@@H:51]([CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:59]([NH2:61])=[O:60])=[O:38])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:12])[CH3:11])([OH:90])=[O:89]

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11953719Phenylalanine amide hydrochlorideHCID 71294483Boc-NMeVal-Val-Dil-Dap2×

Product 1

HCID 56952396N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-amino-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

Procedure

First, the amine compound N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-1-tert.-butoxy-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 was produced as sodium trifluoroacetate, analogous to the synthesis described in example 10, 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 L-phenylalaninamide-hydrochloride 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 47 mg (0.049 mmol) of this compound 39 mg (96% o. th.) of the title compound were obtained in analogy to the production of example 6, treated with 4-ketobutyric acid in the presence of sodium cyanoborohydride.

Sources & evidence

ORD record
ord-085296c3da1346dfbbe457ff015ad32f
Source dataset
uspto-grants-2015_03
Patent number
US08987209B2

Reaction notes

Loading…