Diisopropylethylamine → HCID 76901834, compound
Reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[O:6][CH2:7][C:8]([OH:10])=O)#[N:2].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>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[O:6][CH2:7][C:8]([NH: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)=[O:10])#[N:2]Participants
Conditions
- Temperature
- 25 °C
Procedure
To a stirred mixture of 2-(3-cyanophenoxy)acetic acid (100 mg, 0.565 mmol) in DCM (5 mL) was added DIEA (109 mg, 0.85 mmol), 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (116 mg, 0.565 mmol) and BopCl (173 mg, 0.678 mmol). The resulting mixture was stirred at 25° C. for 16 hours until LCMS showed the completion of the reaction. The reaction mixture was quenched by addition of water (20 mL) then extracted with DCM (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified by prep-HPLC to afford the desired final product (24 mg, Yield 12%). 1H NMR (400 MHz, METHANOL-d4) δ 7.48 (dd, J1=J2=7.6 Hz, 1H), 7.37 (d, J=7.6 Hz, 1H), 7.25-7.21 (m, 2H), 7.13-7.03 (m, 4H), 4.60 (s, 2H), 4.04-4.00 (m, 1H), 3.71 (s, 2H), 3.44 (d, J=6.0 Hz, 2H), 2.93-2.80 (m, 4H), 2.62 (d, J=5.6 Hz, 2H). LCMS (m/z): 366.1 (M+1).
Workup
- customthe completion of the reaction
- customThe reaction mixture was quenched by addition of water (20 mL)
- extractionthen extracted with DCM (3×20 mL)
- washThe combined organic 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-1b0fbf7ea18f4364b2d63f72d71ddabb
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08940726B2
Reaction notes
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