3-acetamidophenoxyacetic acid → HCID 90240885, compound

HRID 1777125Notes

Reaction equation

[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][CH:15]=1)[O:8][CH2:9][C:10]([OH:12])=O)(=[O:3])[CH3:2].[NH2:16][CH2:17][CH:18]([OH:30])[CH2:19][N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:13]=[CH:14][CH:15]=1)[O:8][CH2:9][C:10]([NH:16][CH2:17][CH:18]([OH:30])[CH2:19][N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21]1)=[O:12])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 25 °C

Procedure

To a stirred mixture of 2-(3-acetamidophenoxy) acetic acid (85 mg, 0.41 mmol) in DCM (5 mL) was added TEA (0.5 mL), 1-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (83.8 mg, 0.41 mmol) and HATU (171 mg, 0.451 mmol). The mixture was stirred at 25° C. for 3 hours. The reaction mixture was quenched by addition of water (20 mL) and extracted with DCM (3×20 mL) and the combined extracts washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified by prep-HPLC to afford the title product (55 mg, Yield 35%). 1H NMR (400 MHz, MeOD) δ=7.36 (s, 1H), 7.27-7.17 (m, 1H), 7.19-7.01 (m, 6H), 6.68-6.66 (m, 1H), 4.53 (s, 2H), 4.03-4.00 (m, 1H), 3.71-3.62 (m, 2H), 3.50-3.35 (m, 2H), 2.95-2.85 (m, 2H), 2.83-2.74 (m, 2H), 2.56 (d, J=6.3 Hz, 2H), 2.12 (s, 3H). LCMS (m/z): 398.1 (M+1).

Workup

customThe reaction mixture was quenched by addition of water (20 mL)
extractionextracted with DCM (3×20 mL)
washthe combined extracts washed with brine (20 mL)
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated
customThe residue was purified by prep-HPLC

Sources & evidence

ORD record: ord-c6a1ec8e3f3046f9a3e9bc81af96eff8
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266836B2

Reaction notes

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