Dichloromethane → (R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid 2,2,3,3,3-pentafluoropropyl Ester

HRID 541509Notes

Reaction equation

HRID 541509 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:37])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]([CH2:31][C@@H:32]([OH:36])[C:33]([OH:35])=[O:34])[NH:16][C:17]([C:19]3[O:23][N:22]=[C:21]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=4[F:30])[CH:20]=3)=[O:18])=[CH:10][CH:9]=2)[CH:7]=1.CCN=C=NCCCN(C)C.Cl.C1C=C2N=NN(O)C2=CC=1.O.C(Cl)Cl.[F:64][C:65]([F:72])([C:68]([F:71])([F:70])[F:69])[CH2:66]O>>[F:64][C:65]([F:72])([C:68]([F:71])([F:70])[F:69])[CH2:66][O:34][C:33](=[O:35])[C@H:32]([OH:36])[CH2:31][N:15]([CH2:14][C:11]1[CH:12]=[CH:13][C:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[F:37])=[CH:9][CH:10]=1)[NH:16][C:17]([C:19]1[O:23][N:22]=[C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[F:30])[CH:20]=1)=[O:18]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 98722,2,3,3,3-PentafluoropropanolHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67973214(R)-3-{N-(5'-chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid

Product 1

HCID 86705089(R)-3-{N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)-N'-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid 2,2,3,3,3-pentafluoropropyl EsterYield 12.8%

Procedure

A mixture of (R)-3-{N-(5′-chloro-2′-fluorobiphenyl-4-ylmethyl)-N′-[3-(2-fluorophenyl)isoxazole-5-carbonyl]hydrazino}-2-hydroxypropionic acid (30.0 mg, 57 μmol), EDC HCl (65.4 mg, 341 μmol), and HOBt hydrate (52.2 mg, 341 μmol) in DCM (0.5 mL, 8 mmol) was stirred at room temperature for 10 minutes. 2,2,3,3,3-Pentafluoro-1-propanol (45.3 μL, 455 μmol) was added and the resulting mixture was stirred at room temperature for 1 hour then concentrated. The residue was dissolved in AcOH (2 mL), filtered, and purified by reverse phase prep HPLC to yield the title compound (4.8 mg, purity 90.2%) as a TFA salt. MS m/z [M+H]+ calc'd for C29H21ClF7N3O5, 660.11. found 660.3.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 1 hour
  2. concentrationthen concentrated
  3. dissolutionThe residue was dissolved in AcOH (2 mL)
  4. filtrationfiltered
  5. custompurified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-c560702cc79f4d74b840e9833c2639ec
Source dataset
uspto-grants-2014_10
Patent number
US08871792B2

Reaction notes

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