Hydrochloric Acid → HCID 59608147, compound

HRID 1469632Notes

Reaction equation

HRID 1469632 reaction equation
[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:17][C:18]([C:20]2[S:24][C:23]([O:25]C)=[N:22][CH:21]=2)=[O:19])[CH2:9][C@@H:10]([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:3][CH:2]=1.Cl>O1CCOCC1>[C:1]1([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:17][C:18]([C:20]2[S:24][C:23](=[O:25])[NH:22][CH:21]=2)=[O:19])[CH2:9][C@@H:10]([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:3][CH:2]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 59608216(2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate

Product 1

HCID 59608147HCID 59608147, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of (2R,4S)-ethyl 5-(biphenyl-4-yl)-4-(2-methoxythiazole-5-carboxamido)-2-methylpentanoate, intermediate 19, (171 mg, 0.38 mmol) in dioxane (6 mL) is added 4 M HCl in dioxane (0.25 mL, 1.00 mmol). The crude is stirred at room temperature for 5 hrs. The residue is purified by preparative HPLC using a gradient of MeCN/water (0.1% TFA). The proper fractions are lyophilized to furnish (2R,4S)-ethyl 5-(biphenyl-4-yl)-2-methyl-4-(2-oxo-2,3-dihydrothiazole-5-carboxamido)pentanoate (57 mg). HPLC retention time=1.80 minutes (condition A), MS 439.3 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.17 (d, J=7.1 Hz, 3 H), 1.23 (t, J=7.2 Hz, 3 H), 1.67 (ddd, J=14.0, 10.0, 3.5 Hz, 1 H), 1.85-2.03 (m, 1 H), 2.51-2.69 (m, 1 H), 2.77-2.91 (m, 1 H), 2.93-3.05 (m, 1 H), 4.13 (q, J=7.1 Hz, 2 H), 4.26-4.42 (m, 1 H), 5.97 (d, J=8.1 Hz, 1 H), 7.17-7.29 (m, 2 H) 7.29-7.37 (m, 1 H) 7.42 (t, J=7.6 Hz, 2 H) 7.53 (d, J=7.8 Hz, 2 H) 7.57 (d, J=8.1 Hz, 2 H) 9.46 (br. s., 1 H).

Workup

  1. customThe residue is purified by preparative HPLC

Sources & evidence

ORD record
ord-0865cb30253449398303ebe847dac133
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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