Tetraethyl methylenediphosphonate → (E)-diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)vinylphosphonate

HRID 2167652Notes

Reaction equation

[H-].[Na+].[CH2:3]([P:12](=[O:19])([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])P(=O)(OCC)OCC.[NH2:20][C:21]1[C:30]2[N:29]=[CH:28][C:27]([CH2:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][C:34]=3[CH3:41])=[CH:26][C:25]=2[C:24]2[CH:42]=[CH:43][C:44]([CH:46]=O)=[CH:45][C:23]=2[N:22]=1>C1COCC1>[NH2:20][C:21]1[C:30]2[N:29]=[CH:28][C:27]([CH2:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][C:34]=3[CH3:41])=[CH:26][C:25]=2[C:24]2[CH:42]=[CH:43][C:44](/[CH:46]=[CH:3]/[P:12](=[O:19])([O:13][CH2:14][CH3:15])[O:16][CH2:17][CH3:18])=[CH:45][C:23]=2[N:22]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred suspension of NaH (1.2 equiv.) in THF (0.1 M) cooled at 0° C. was added a solution of tetraethyl methylenediphosphonate (1.3 equiv.) in THF (0.21 M). To the resulting reaction mixture was added a solution of 5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridine-8-carbaldehyde (2-2) (Example 9—Step 1) (1.0 equiv.) in THF (0.08 M). The reaction was stirred at room temperature for 30 minutes, then solvents were removed in vacuo, and the resulting residue was purified by a COMBIFLASH® system (ISCO) using a gradient of 0-5% MeOH/DCM to provide (E)-diethyl 2-(5-amino-2-(4-methoxy-2-methylphenethyl)benzo[f][1,7]naphthyridin-8-yl)vinylphosphonate (3-1) as a colorless solid.

Workup

customTo the resulting reaction mixture
customsolvents were removed in vacuo
customthe resulting residue was purified by a COMBIFLASH® system (ISCO)

Sources & evidence

ORD record: ord-6054d67dffec407ea3325d3b880e74a5
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09045470B2

Reaction notes

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