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

HRID 882603Notes

Reaction equation

HRID 882603 reaction equation
C(OC([N:8]([CH3:48])[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.[NH:49]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[C:51]([CH2:58][CH2:59][NH2:60])=[CH:50]1.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.FC(F)(F)C([O-])=O.O=[CH:100][CH2:101][CH2:102][C:103]([OH:105])=[O:104].C([BH3-])#N.[Na+]>>[C:103]([CH2:102][CH2:101][CH2:100][N:8]([CH3:48])[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:60][CH2:59][CH2:58][C:51]1[C:52]2[C:57](=[CH:56][CH:55]=[CH:54][CH:53]=2)[NH:49][CH:50]=1)=[O:38])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:11])[CH3:12])([OH:105])=[O:104]

Participants

8

Reactant 7

HCID 11124-Oxobutanoic acidHCID 1150TryptamineHCID 6422Trifluoroacetic acidHCID 84468TrifluoroacetateHCID 5003444Sodium cyanoborohydrideHCID 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×

Product 1

HCID 66548075N-(3-carboxypropyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(1H-indol-3-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Procedure

First, in analogy to the synthesis described in Intermediate 74, by coupling of 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) and 2-(1H-indol-3-yl)ethanamine 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, the amine compound N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-3-{[2-(1H-indol-3-yl)ethyl]amino}-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide was prepared as the trifluoroacetate. 100 mg (0.119 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 50 mg (49% of theory) of the title compound. The title compound was purified here by flash chromatography on silica gel with dichloromethane/methanol/17% ammonia as the eluent, in the course of which the mixing ratio was switched from initially 15/2/02 to 15/4/0.5.

Sources & evidence

ORD record
ord-58fd286efb6342ccb0e2e0a15c368388
Source dataset
uspto-grants-2015_03
Patent number
US08992932B2

Reaction notes

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