Hydrochloric Acid → HCID 59607856, compound

HRID 881828Notes

Reaction equation

HRID 881828 reaction equation
Cl.[NH2:2][C@H:3]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=2)=[CH:13][CH:12]=1)[CH2:4][C:5]([O:7]CC)=[O:6].[N:24]([CH2:27][C:28]([O:30]CC)=[O:29])=[C:25]=[O:26].N1C=CC=CC=1.[OH-].[Na+].Cl>CN(C=O)C>[C:28]([CH2:27][NH:24][C:25](=[O:26])[NH:2][C@H:3]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=2)=[CH:15][CH:16]=1)[CH2:4][C:5]([OH:7])=[O:6])([OH:30])=[O:29]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 14798Sodium HydroxideHCID 76283Ethyl isocyanatoacetate2×HCID 86648190(R)-ethyl 3-amino-4-(3'-chlorobiphenyl-4-yl)butanoate hydrochloride

Product 1

HCID 59607856HCID 59607856, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Intermediate 8-1 (90 mg, 0.254 mmol) and ethyl isocyanatoacetate (Intermediate 16-1: 39.4 mg, 0.305 mmol) in DMF (3 mL) is added pyridine (2.93 g, 37.1 mmol) and the mixture is stirred at room temperature for 2 hours. The solvent is removed under reduced pressure and the residue is used directly in the next step. Next, the above residue is dissolved in EtOH (1 mL) and 1N NaOH (3 mL, 3 mmol) is added. The mixture is stirred at room temperature for 2 hours then is acidified with 1N HCl. The mixture is extracted with EtOAc and the organic phase is washed with water, brine then dried over sodium sulfate. The solvent is removed under reduced pressure and the residue purified by preparative HPLC using a gradient of 10% MeCN/water to 100% MeCN (+0.1% TFA). Lyophilization of the proper fractions gives the title compound; HPLC Retention time 0.98 minutes (condition C); MS 391.3 (M+1); 1H NMR (400 MHz, DMSO-d6): δ ppm 2.34 (d, J=7.33 Hz, 2H), 2.79 (d, J=6.57 Hz, 2H), 3.67 (d, J=5.56 Hz, 2H), 4.04-4.12 (m, 1H), 6.15 (t, J=5.81 Hz, 1H), 6.23 (d, J=8.34 Hz, 1H), 7.28-7.30 (m, 2H), 7.39-7.42 (m, 1H), 7.48 (t, J=7.83 Hz, 1H), 7.62-7.65 (m, 3H), 7.71 (t, J=1.77 Hz, 1H), 12.32 (s, br, 2H).

Workup

  1. customThe solvent is removed under reduced pressure
  2. dissolutionNext, the above residue is dissolved in EtOH (1 mL)
  3. stirringThe mixture is stirred at room temperature for 2 hours
  4. extractionThe mixture is extracted with EtOAc
  5. washthe organic phase is washed with water, brine
  6. dry with materialthen dried over sodium sulfate
  7. customThe solvent is removed under reduced pressure
  8. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-84c8dbf2bc754606b278c535fcafcb1e
Source dataset
uspto-grants-2015_03
Patent number
US08993631B2

Reaction notes

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