Triethyl phosphonoacetate → HCID 44231886, compound

HRID 340276Notes

Reaction equation

HRID 340276 reaction equation
[H-].[Na+].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.[NH2:17][C:18]1[C:27]2[N:26]=[CH:25][C:24]([CH2:28][CH2:29][C:30]3[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][C:31]=3[CH3:38])=[CH:23][C:22]=2[C:21]2[CH:39]=[CH:40][C:41]([CH3:43])=[CH:42][C:20]=2[N:19]=1>C1COCC1>[NH2:17][C:18]1[C:27]2[N:26]=[CH:25][C:24]([CH2:28][CH2:29][C:30]3[CH:37]=[CH:36][C:33](/[CH:34]=[CH:11]/[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:32][C:31]=3[CH3:38])=[CH:23][C:22]=2[C:21]2[CH:39]=[CH:40][C:41]([CH3:43])=[CH:42][C:20]=2[N:19]=1

Participants

5

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 86652353HCID 86652353, compound

Product 1

HCID 44231886HCID 44231886, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of NaH (3 eq) in THF (0.2 M) stirred at 0° C. was added ethyl 2-(diethoxyphosphoryl)acetate (commercially available) (3 eq). After stirring for 30 minutes, a solution of 4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylbenzaldehyde (from the previous step) in THF (0.2 M) was added dropwise. The reaction was allowed to warm to room temperature and stirred overnight. The reaction was quenched with sat. NH4Cl solution, and was extracted with EtOAc. Combined organic extracts were dried and concentrated to give a crude residue which was purified by chromatography (silica gel, 50-100% EtOAc in hexanes) to afford (E)-ethyl 3-(4-(2-(5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethyl)-3-methylphenyl)acrylate as a white solid. 1H NMR: (CDCl3): δ 8.54 (d, 1H), 8.29 (d, 1H), 7.99 (d, 1H), 7.57 (d, 1H), 7.44 (s, 1H), 7.23 (dd, 1H), 7.11 (dd, 1H), 7.05 (d, 1H), 6.33 (d, 1H), 5.93 (s, 2H), 4.19 (q, 2H), 3.10-2.95 (m, 4H), 2.44 (s, 3H), 2.23 (s, 3H), 1.26 (t, 3H). LRMS [M+H]=426.2

Workup

  1. stirringAfter stirring for 30 minutes
  2. temperatureto warm to room temperature
  3. stirringstirred overnight
  4. customThe reaction was quenched with sat. NH4Cl solution
  5. extractionwas extracted with EtOAc
  6. customCombined organic extracts were dried
  7. concentrationconcentrated
  8. customto give a crude residue which
  9. customwas purified by chromatography (silica gel, 50-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-489b510c84574cd68a4db29b3fe40471
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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