Water → HCID 178523854, compound

HRID 516458Notes

Reaction equation

HRID 516458 reaction equation
[OH:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[N:5]=[C:4]([C:13]([OH:15])=O)[CH:3]=1.CN(C(ON1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.CC1OC(=O)OC=1C[O:54][C:55](=[O:75])[C@H:56]([OH:74])[CH2:57][C@H:58]([NH2:73])[CH2:59][C:60]1[CH:65]=[CH:64][C:63]([C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([Cl:72])[CH:67]=2)=[CH:62][CH:61]=1.CCN(C(C)C)C(C)C.[Li+].[OH-].O>>[Cl:72][C:68]1[CH:67]=[C:66]([C:63]2[CH:62]=[CH:61][C:60]([CH2:59][C@@H:58]([NH:73][C:13]([C:4]3[CH:3]=[C:2]([OH:1])[N:6]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=4)[N:5]=3)=[O:15])[CH2:57][C@@H:56]([OH:74])[C:55]([OH:75])=[O:54])=[CH:65][CH:64]=2)[CH:71]=[CH:70][CH:69]=1

Participants

8

Reactant 7

HCID 962WaterHCID 3939Lithium HydroxideHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 86705143(2R,4R)-4-Amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo[1,3]dioxol-4-ylmethyl esterHCID 178524632HCID 178524632, compound

Product 1

HCID 178523854HCID 178523854, compoundYield 58.4%

Procedure

5-Hydroxy-1-pyridin-2-yl-1H-pyrazole-3-carboxylic acid (59.0 mg, 287 μmol) and HCTU (131 mg, 316 μmol) were combined in DMF (1.3 mL, 17.2 mmol). and stirred at room temperature for 15 minutes. (2R,4R)-4-amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo[1,3]dioxol-4-ylmethyl ester (100 mg, 0.3 mmol) and DIPEA (150 μL, 862 μmol) were added, and the resulting mixture was stirred at room temperature for 15 minutes. The reaction was evaporated under reduced pressure. The residue was dissolved in EtOH and a solution of 1 M LiOH in water (1.4 mL, 1.4 mmol) was added. The resulting mixture was stirred at room temperature for 1 hour, then evaporated under reduced pressure. The residue was purified by preparative HPLC to yield the title compound (85 mg). MS m/z [M+H]+ calc'd for C26H23ClN4O5, 507.14. found 507.1.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 15 minutes
  2. customThe reaction was evaporated under reduced pressure
  3. dissolutionThe residue was dissolved in EtOH
  4. stirringThe resulting mixture was stirred at room temperature for 1 hour
  5. customevaporated under reduced pressure
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ce0445d45c554fd1a3e844e7cd261934
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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