Hydrochloric Acid → HCID 59607574, compound

HRID 70892Notes

Reaction equation

HRID 70892 reaction equation
[CH3:1][O:2][C:3]1[S:4][C:5]([C:8]([OH:10])=O)=[CH:6][N:7]=1.Cl.[NH2:12][C@H:13]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[CH:28]=2)=[CH:23][CH:22]=1)[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.O.CCOC(C)=O>[Cl:33][C:29]1[CH:28]=[C:27]([C:24]2[CH:25]=[CH:26][C:21]([CH2:20][C@@H:13]([NH:12][C:8]([C:5]3[S:4][C:3]([O:2][CH3:1])=[N:7][CH:6]=3)=[O:10])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:22][CH:23]=2)[CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 164948972-Methoxy-1,3-thiazole-5-carboxylic acidHCID 86648190(R)-ethyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate hydrochloride

Product 1

HCID 59607574HCID 59607574, compoundYield 82.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-methoxythiazole-5-carboxylic acid (80 mg, 0.50 mmol) and (R)-ethyl 3-amino-4-(3′-chlorobiphenyl-4-yl)butanoate hydrochloride (160 mg, 0.45 mmol) in DMF (5 mL) is added HATU (207 mg, 0.55 mmol) and TEA (276 mg, 2.73 mmol). The crude is stirred at room temperature for 2 hrs. The crude is neutralized with 1 N HCl and diluted in water and EtOAc. The organic layer is washed with brine, dried over MgSO4, filtered, and concentrated. The crude is purified via flash chromatography using 30% EtOAc/heptane to 70% EtOAc/heptane to give (R)-ethyl 4-(3′-chlorobiphenyl-4-yl)-3-(2-methoxythiazole-5-carboxamido)butanoate (170 mg). HPLC retention time=1.97 minutes (condition D); MS (m+1)=459.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.29 (t, J=7.1 Hz, 3 H) 2.49-2.69 (m, 2 H) 2.93 (dd, J=13.6, 8.1 Hz, 1 H) 3.10 (dd, J=13.5, 6.2 Hz, 1 H) 4.09 (s, 3 H) 4.00-4.15 (m, 2 H) 4.53-4.69 (m, 1 H) 6.78 (d, J=8.6 Hz, 1 H) 7.25-7.32 (m, 3 H) 7.35 (t, J=7.71 Hz, 1 H) 7.44 (dt, J=7.6, 1.5 Hz, 1 H) 7.48-7.54 (m, 3 H) 7.55 (t, J=1.8 Hz, 1 H).

Workup

  1. washThe organic layer is washed with brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude is purified via flash chromatography

Sources & evidence

ORD record
ord-7d3b97b771f64bd793fb18336a4b5bb4
Source dataset
uspto-grants-2014_09
Patent number
US08822534B2

Reaction notes

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