Dimethylacetamide → HCID 86705104, compound

HRID 541526Notes

Reaction equation

HRID 541526 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:10]([CH3:12])[CH3:11])[C:7]([OH:9])=[O:8])=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC(N(C)C)=O.[Cl:43][C:44]1[CH:45]=[CH:46][C:47]([F:74])=[C:48]([C:50]2[CH:55]=[CH:54][C:53]([CH2:56][N:57]([CH2:68][C@@H:69](O)[C:70]([OH:72])=[O:71])[NH:58][C:59]([C:61]3[O:65][N:64]=[C:63]([O:66][CH3:67])[CH:62]=3)=[O:60])=[CH:52][CH:51]=2)[CH:49]=1.CCN(C(C)C)C(C)C>>[C:70]([C@H:69]([O:8][C:7](=[O:9])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[CH:10]([CH3:12])[CH3:11])[CH2:68][N:57]([CH2:56][C:53]1[CH:54]=[CH:55][C:50]([C:48]2[CH:49]=[C:44]([Cl:43])[CH:45]=[CH:46][C:47]=2[F:74])=[CH:51][CH:52]=1)[NH:58][C:59]([C:61]1[O:65][N:64]=[C:63]([O:66][CH3:67])[CH:62]=1)=[O:60])([OH:72])=[O:71]

Participants

6

Reactant 5

HCID 31374DimethylacetamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10942966(2S)-2-((methoxycarbonyl)amino)-3-methylbutanoic acidHCID 67972936(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic Acid

Product 1

HCID 86705104HCID 86705104, compoundYield 20.1%

Procedure

(S)-2-Methoxycarbonylamino-3-methylbutyric acid (5.7 mg, 32.3 μmol) and HATU (12.3 mg, 32.3 μmol) were stirred in DMA (1.0 mL, 11 mmol) for 15 minutes. (R)-3-[N-(5′-Chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-(3-methoxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid (10.0 mg, 21.6 μmol) and DIPEA (11.3 μL, 64.7 μmol) were added, and the resulting mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was dissolved in AcOH (1.5 mL), filtered, and purification by reverse phase preparative HPLC to yield the title compound (2.7 mg). MS m/z [M+H]+ calc'd for C28H30ClFN4O9, 621.17. found 621.3.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in AcOH (1.5 mL)
  3. filtrationfiltered
  4. custompurification by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-bc08632f878746d4a06d1d5f39d7a38e
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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