Dimethylformamide → (5-Chloro-6-phenylethynyl-1H-benzoimidazol-2-ylsulfanylmethyl)-phosphonic acid diethyl ester

HRID 2193852Notes

Reaction equation

[CH2:1]([O:3][P:4]([CH2:9][S:10][C:11]1[NH:15][C:14]2[CH:16]=[C:17]([Cl:21])[C:18](I)=[CH:19][C:13]=2[N:12]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[C:22]1([C:28]#[CH:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.CCN(CC)CC.CN(C=O)C>CCOC(C)=O.[Cu]I>[CH2:1]([O:3][P:4]([CH2:9][S:10][C:11]1[NH:12][C:13]2[CH:19]=[C:18]([C:29]#[C:28][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:17]([Cl:21])=[CH:16][C:14]=2[N:15]=1)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of (6-Chloro-5-iodo-1H-benzoimidazol-2-ylsulfanylmethyl)-phosphonic acid diethyl ester (Intermediate 1, 0.4 g, 1.0 mmol), phenyl acetylene (0.26 mL, 2.0 mmol), PdCl(PPh3)2 (0.34 g, 0.050 mmol), CuI (0.018 g, 0.1 mmol), Et3N (0.96 mL, 6.94 mmol), and 10.0 mL of DMF was heated to 120° C. for 10 minutes using a microwave reactor. HPLC indicated the reaction was complete. The crude mixture was diluted with 40 mL EtOAc and washed with 3×40 mL H2O. The organic fractions were separated, combined, dried over MgSO4, and concentrated in vacuo to afford an oil. This oil was purified by MPLC to afford title compound 1-1 as clear oil.

Workup

washwashed with 3×40 mL H2O
customThe organic fractions were separated
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customto afford an oil
customThis oil was purified by MPLC

Sources & evidence

ORD record: ord-fffab433764244fda1c96a2cb2a9e472
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329914B2

Reaction notes

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