2-(3-Methoxyphenoxy)acetic acid → N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-(3-methoxyphenoxyl)acetamide
Reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[O:6][CH2:7][C:8]([OH:10])=O.CCN(C(C)C)C(C)C.[NH2:23][CH2:24][CH:25]([OH:37])[CH2:26][N:27]1[CH2:36][CH2:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:28]1.C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1>C(Cl)Cl>[CH2:28]1[C:29]2[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:35][CH2:36][N:27]1[CH2:26][CH:25]([OH:37])[CH2:24][NH:23][C:8](=[O:10])[CH2:7][O:6][C:5]1[CH:11]=[CH:12][CH:13]=[C:3]([O:2][CH3:1])[CH:4]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 25 °C
Procedure
To a stirred mixture of 2-(3-methoxyphenoxy)acetic acid (100 mg, 0.549 mmol) in DCM (5 mL) was added DIEA (106 mg, 0.824 mmol), 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (113 mg, 0.549 mmol) and Bop-Cl (168 mg, 0.66 mmol). The mixture was stirred at 25° C. for 16 hours then the reaction mixture was quenched with water (20 mL), extracted with DCM (3×20 mL). The combined extracts were washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified by prep-HPLC to afford the desired product (61 mg, Yield 32%). 1H NMR (400 MHz, MeOD) δ 7.21 (dd, J1=J2=8.0 Hz, 1H), 7.17-7.03 (m, 4H), 6.59-6.51 (m, 3H), 4.52 (s, 2H), 4.05-4.01 (m, 1H), 3.77 (s, 3H), 3.73 (d, J=2.8 Hz, 2H), 3.47-3.37 (m, 2H), 2.92 (d, J=5.2 Hz, 2H), 2.87 (d, J=5.2 Hz, 2H), 2.61 (d, J=6.0 Hz, 2H). LCMS (m/z): 371.1 (M+1).
Workup
- customthe reaction mixture was quenched with water (20 mL)
- extractionextracted with DCM (3×20 mL)
- washThe combined extracts were washed with brine (20 mL)
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated
- customThe residue was purified by prep-HPLC
Sources & evidence
- ORD record
- ord-fbb60725d6f34f0e87664cdaa27b4857
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08940726B2
Reaction notes
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