Hydrochloric Acid → HCID 66934465, compound

HRID 1365505Notes

Reaction equation

HRID 1365505 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@:8]([C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([F:30])[CH:21]=2)([NH:13]C(=O)C(C)(C)C)[CH2:9][C:10]([OH:12])=O)=[N:6][CH:7]=1.Cl.[NH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CO.C(#N)C.CO.O>[NH2:13][C@:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=1)([C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:23]=[C:22]([F:30])[CH:21]=1)[CH2:9][C:10]([NH:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:12]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 2733179PyBroPHCID 66934634HCID 66934634, compound

Product 1

HCID 66934465HCID 66934465, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

(S)-3-(5-chloropyridin-2-yl)-3-(3-fluoro-5-(trifluoromethyl)phenyl)-3-pivalamidopropanoic acid (0.10 g, 0.21 mmol) was dissolved in MeOH (2 mL) and 4M HCl in dioxanes added (2 mL). The resulting solution was stirred at RT for 30 mins then the solvents were removed under reduced pressure yielding a pale yellow oil (crude quantative) LCMS: 1.31 min [M+1] 363.2 (2 min gradient, MeOH/H2O 0.1% TFA). The residue was dissolved in acetonitrile (5 mL) and TEA, (0.3 mL, excess), aniline (0.030 g, 0.32 mmol) and PyBrOP (0.11 g, 0.24 mmol) added at RT. The RM was stirred for 14 h, concentrated to 1.5 mL, filtered and purified by prep HPLC: YMC ODSA30×100 mm, 40ml/min, 20-100% MeOH (0.1% TFA) over 10 min. The product (S)-3-amino-3-(5-chloropyridin-2-yl)-3-(3-fluoro-5-(trifluoromethyl)phenyl)-N-phenylpropanamide with a retention time of 7.52 min was isolated as a pale yellow oil, (0.054 g, 58% yield). LCMS: 1.48 min [M+1] 438.2 (2 min gradient, MeOH/H2O 0.1% TFA).

Workup

  1. customthe solvents were removed under reduced pressure
  2. customyielding a pale yellow oil (crude quantative)
  3. stirringThe RM was stirred for 14 h
  4. concentrationconcentrated to 1.5 mL
  5. filtrationfiltered
  6. custompurified by prep HPLC
  7. waitYMC ODSA30×100 mm, 40ml/min, 20-100% MeOH (0.1% TFA) over 10 min

Sources & evidence

ORD record
ord-6640dede3ac64167ad42dc9fe066e5a9
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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