1-Bromopropane → 2-(1,1'-biphenyl-4-yl)-N-[(1R)-1-(5-propoxypyridin-2-yl)ethyl]acetamide

HRID 254702Notes

Reaction equation

[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:6]=[CH:5][C:4]([CH2:7][C:8]([NH:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][N:14]=2)[CH3:12])=[O:9])=[CH:3][CH:2]=1.Br[CH2:27][CH2:28][CH3:29].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:1]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:2]=[CH:3][C:4]([CH2:7][C:8]([NH:10][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:27][CH2:28][CH3:29])=[CH:15][N:14]=2)[CH3:12])=[O:9])=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 40 °C

Procedure

To a mixture of 2-(1,1′-biphenyl-4-yl)-N-[(1R)-1-(5-hydroxypyridin-2-yl)ethyl]acetamide (30 mg, 0.09 mmol) (Example 8), 1-bromopropane (0.02 ml, 0.22 mmol) in DMF (1.2 ml) was added potassium carbonate (37 mg, 0.27 mmol). The reaction was stirred at 40° C. for 18 hours and then filtered through a cotton plug to remove any precipitates, washing with DMSO (2 ml). The collected filtrate was purified using reverse phase prep HPLC chromatography to afford the mono-trifluoroacetate salt of 2-(1,1′-biphenyl-4-yl)-N-[(1R)-1-(5-propoxypyridin-2-yl)ethyl]acetamide as an oil. 1H NMR (CD3OD, 400 MHz) δ 8.34 (s, 1H); 7.97 (dd, J=2.80 and 9.20 Hz, 1H); 7.74 (d, J=8.80 Hz, 1H); 7.56 (m, 4H); 7.40 (m, 2H); 7.33 (m, 3H); 5.07 (m, 1H); 4.11 (t, J=6.40 Hz, 2H); 3.61 (s, 2H); 1.84 (m, 2H); 1.57 (d, J=7.20 Hz, 3H); 1.05 (t, J=7.60 Hz, 3H). HRMS (ES) exact mass calcd for C24H26N2O2: 375.2067, Found: 375.2078.

Workup

filtrationfiltered through a cotton plug
customto remove any precipitates
washwashing with DMSO (2 ml)
customThe collected filtrate was purified

Sources & evidence

ORD record: ord-0e51bd1e450c4e50a9623eb280bb6def
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875636B2

Reaction notes

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