Sodium Bicarbonate → 1-(3-(1H-benzo[d]imidazol-4-yl)phenoxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol

HRID 1399891Notes

Reaction equation

[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:38])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]2[C:29]3[N:28]=[CH:27][N:26](COCC[Si](C)(C)C)[C:25]=3[CH:24]=[CH:23][CH:22]=2)[CH:16]=1.C([O-])(O)=O.[Na+]>CCO.Cl>[NH:26]1[C:25]2[CH:24]=[CH:23][CH:22]=[C:21]([C:17]3[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=3)[O:14][CH2:13][CH:12]([OH:38])[CH2:11][N:2]3[CH2:3][CH2:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH2:1]3)[C:29]=2[N:28]=[CH:27]1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-benzo[d]imidazol-4-yl)phenoxy)propan-2-ol (265 mg, 0.5 mmol) in EtOH (20 mL) and conc. HCl (1 mL) was stirred at 80° C. overnight. The reaction was adjusted to pH 9 by aq. NaHCO3. The mixture was then extracted with DCM and the combined organic layers dried over Na2SO4 and concentrated to give the crude product. The crude product was purified by pre-HPLC to afford the desired product (50 mg, Yield 25%). 1H NMR (400 MHz, DMSO-d6) δ 8.43 (s, 1H), 8.35 (s, 2H), 7.65 (br.s, 2H), 7.49 (m, 1H), 7.21 (dd, J=7.6 Hz, 1H), 7.12-7.06 (m, 5H), 4.53-4.39 (m, 3H), 4.14 (s, 2H), 2.83-2.57 (m, 6H). LCMS (m/z): 400.1 (M+1).

Workup

extractionThe mixture was then extracted with DCM
dry with materialthe combined organic layers dried over Na2SO4
concentrationconcentrated
customto give the crude product
customThe crude product was purified by pre-HPLC

Sources & evidence

ORD record: ord-c96c3b16378448c4aeea56747b3ce87d
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906900B2

Reaction notes

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