Acetic Acid → HCID 178502507, compound

HRID 541554Notes

Reaction equation

HRID 541554 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.C(Cl)Cl.O=C(C1C=CC=CC=1)C[O:43][C:44](=[O:72])[C@H:45](O)[CH2:46][N:47]([CH2:57][C:58]1[CH:63]=[CH:62][C:61]([C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([Cl:70])[CH:65]=2)=[CH:60][CH:59]=1)[NH:48][C:49]([C:51]1[O:55][N:54]=[C:53]([OH:56])[CH:52]=1)=[O:50].CCN(C(C)C)C(C)C.CC(O)=O>[Zn]>[C:44]([C@H:45]([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])[CH2:46][N:47]([CH2:57][C:58]1[CH:63]=[CH:62][C:61]([C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([Cl:70])[CH:65]=2)=[CH:60][CH:59]=1)[NH:48][C:49]([C:51]1[O:55][N:54]=[C:53]([OH:56])[CH:52]=1)=[O:50])([OH:72])=[O:43]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 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 178521475HCID 178521475, compound

Product 1

HCID 178502507HCID 178502507, compoundYield 3.7%

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst

Procedure

(S)-2-Methoxycarbonylamino-3-methylbutyric acid (9.6 mg, 54.5 μmol) and HATU (23.5 mg, 62 μmol) were stirred in DCM (1.0 mL, 16 mmol) for 10 minutes. (R)-3-[N-(3′-Chlorobiphenyl-4-ylmethyl)-N′-(3-hydroxyisoxazole-5-carbonyl)hydrazino]-2-hydroxypropionic acid 2-oxo-2-phenylethyl ester (20.0 mg, 36.4 μmol) and DIPEA (31.7 μL, 182 μmol) were added, and the resulting mixture was stirred at room temperature overnight. The mixture was then concentrated and purified by flash chromatography (EtOAc/hexanes=0-100%). Zinc (119 mg, 1.8 mmol) and AcOH (0.5 mL, 9 mmol) were added. The mixture was stirred for 2 hours and filtered. The solids were washed with AcOH (1 mL) and filtered. The combined filtrates were purified by reverse phase preparative HPLC to yield the title compound (0.8 mg). MS m/z [M+H]+ calc'd for C27H29ClN4O9, 589.16. found 589.3.

Workup

  1. concentrationThe mixture was then concentrated
  2. custompurified by flash chromatography (EtOAc/hexanes=0-100%)
  3. stirringThe mixture was stirred for 2 hours
  4. filtrationfiltered
  5. washThe solids were washed with AcOH (1 mL)
  6. filtrationfiltered
  7. customThe combined filtrates were purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-2b788c461d3c4007b4b1a6a6c68f88fb
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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