1,2-Dichloroethane → (R)-3-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid 5-Methyl-2-oxo-[1,3]-dioxol-4-ylmethyl Ester

HRID 541541Notes

Reaction equation

HRID 541541 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:9]([NH:11][N:12]([CH2:28][C@@H:29]([OH:33])[C:30]([OH:32])=[O:31])[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[F:27])=[CH:16][CH:15]=2)=[O:10])[NH:7][N:8]=1)(=[O:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(Cl)Cl.O[CH2:52][C:53]1[O:54][C:55](=[O:59])[O:56][C:57]=1[CH3:58].CN1CCOCC1>>[CH3:58][C:57]1[O:56][C:55](=[O:59])[O:54][C:53]=1[CH2:52][O:31][C:30](=[O:32])[C@H:29]([OH:33])[CH2:28][N:12]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=2[F:27])=[CH:16][CH:15]=1)[NH:11][C:9]([C:6]1[NH:7][N:8]=[C:4]([C:1](=[O:3])[CH3:2])[CH:5]=1)=[O:10]

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 6344DichloromethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 105108784-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-oneHCID 86705116(R)-3-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid

Product 1

HCID 117669078(R)-3-[N'-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid 5-Methyl-2-oxo-[1,3]-dioxol-4-ylmethyl EsterYield 1.6%

Procedure

(R)-3-[N′-(5-Acetyl-2H-pyrazole-3-carbonyl)-N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic acid (30.0 mg, 63 mmol), HOBt (26 mg, 190 μmol) and EDC (34 μL, 190 μmol) were combined in DCM (243 μL, 3.8 mmol) and stirred for 10 minutes. 4-Hydroxymethyl-5-methyl-[1,3]dioxol-2-one (66 mg, 0.5 mmol) and 4-methylmorpholine (28 μL, 250 μmol) were added and the resulting mixture was stirred at room temperature for 3 hours. The mixture was evaporated under reduced pressure, yielding a brown oil, which was purified by preparative HPLC to yield the title compound (4.6 mg, purity 97%) as a TFA salt. MS m/z [M+H]+ calc'd for C27H24ClFN4O8, 587.13. found 587.1.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 3 hours
  2. customThe mixture was evaporated under reduced pressure
  3. customyielding a brown oil, which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-8cf47cfb37b94a778a14eb11d998e72b
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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