Trifluoroacetic acid → N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-3-(4-hydroxyphenyl)-1-(1,2-oxazinan-2-yl)-1-oxopropan-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

HRID 882656Notes

Reaction equation

HRID 882656 reaction equation
C(OC([N:8]([CH3:36])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:32]([CH3:35])[CH2:33][CH3:34])[C@H:25]([O:30][CH3:31])[CH2:26][C:27]([OH:29])=O)[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C.[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40].[NH2:44][C@@H:45]([CH2:54][C:55]1[CH:60]=[CH:59]C(O)=C[CH:56]=1)[C:46]([N:48]1[CH2:53][CH2:52][CH2:51][CH2:50][O:49]1)=[O:47].C(OC(N(C)[C@H](C(N[C@H](C(N([C@@H]([C@@H](C)CC)[C@H](OC)CC([N:90]1[CH2:94][CH2:93][CH2:92][C@H:91]1[C@H:95]([O:101][CH3:102])[C@H:96]([C:98](O)=[O:99])[CH3:97])=O)C)=O)C(C)C)=O)C(C)C)=O)(C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.FC(F)(F)C(O)=O>>[F:37][C:38]([F:43])([F:42])[C:39]([OH:41])=[O:40].[CH3:36][NH:8][C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:32]([CH3:35])[CH2:33][CH3:34])[C@H:25]([O:30][CH3:31])[CH2:26][C:27]([N:90]1[CH2:94][CH2:93][CH2:92][C@H:91]1[C@H:95]([O:101][CH3:102])[C@@H:96]([CH3:97])[C:98]([NH:44][C@@H:45]([CH2:54][C:55]1[CH:56]=[CH:38][C:39]([OH:41])=[CH:59][CH:60]=1)[C:46]([N:48]1[CH2:53][CH2:52][CH2:51][CH2:50][O:49]1)=[O:47])=[O:99])=[O:29])[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:11])[CH3:12]

Participants

6

Reactant 5

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 71294483Boc-NMeVal-Val-Dil-Dap2×HCID 86678337HCID 86678337, compoundHCID 86678424HCID 86678424, compound

Product 1

HCID 86678422N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[(2S)-3-(4-hydroxyphenyl)-1-(1,2-oxazinan-2-yl)-1-oxopropan-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

Procedure

First, in analogy to Intermediate 5, trifluoroacetic acid-(2S)-2-amino-3-(4-hydroxyphenyl)-1-(1,2-oxazinan-2-yl)propan-1-one (1:1) was prepared. This reagent was then used, in analogy to the synthesis described in Intermediate 75, by coupling with 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 26) in the presence of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate and subsequent detachment of the Boc protecting group by means of trifluoroacetic acid, to prepare the title compound.

Sources & evidence

ORD record
ord-bfcc74f72834461383d1f6ae6719c608
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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