4-Oxobutanoic acid → HCID 56952496, compound

HRID 882600Notes

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]([OH:39])=O)[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.F[C:50](F)(F)[C:51]([OH:53])=[O:52].[NH2:56][C@@:57]1([C:66]([NH2:68])=[O:67])[CH2:59][C@@H:58]1[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:80]2N=CC=C[C:79]=2N=N1.FC(F)(F)C(O)=O.FC(F)(F)C([O-])=O.O=CCCC(O)=O.C([BH3-])#N.[Na+]>>[C:51]([CH2:50][CH2:79][CH2:80][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:56][C@@:57]1([C:66](=[O:67])[NH2:68])[CH2:59][C@@H:58]1[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1)=[O:39])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:18])[CH3:19])=[O:14])[CH:10]([CH3:12])[CH3:11])([OH:53])=[O:52]

Participants

Reactant 7

HCID 11124-Oxobutanoic acid

HCID 6422Trifluoroacetic acid

HCID 84468Trifluoroacetate

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 71294483Boc-NMeVal-Val-Dil-Dap2×

HCID 71294610HCID 71294610, compound2×

Product 1

HCID 56952496HCID 56952496, compound

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 (1S,2R)-1-amino-2-phenylcyclopropanecarboxamide trifluoroacetate (Intermediate 48) 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-{[(1S,2R)-1-carbamoyl-2-phenylcyclopropyl]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. 14 mg (0.0163 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 8 mg (57% of theory) of the title compound.

Sources & evidence

ORD record: ord-a8ac097ce07d4089b0369596e588d862
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08992932B2

Reaction notes

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