Triethyl phosphite → HCID 58528960, compound

HRID 1430990Notes

Reaction equation

HRID 1430990 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10](=[O:29])[C:11]2[CH:16]=[C:15]([O:17][CH2:18][CH2:19][C:20]3[CH:24]=[CH:23][S:22][CH:21]=3)[CH:14]=[C:13]([O:25][CH:26]([CH3:28])[CH3:27])[CH:12]=2)=[N:7][CH:8]=1.[P:30]([O:37]CC)([O:34][CH2:35][CH3:36])[O:31][CH2:32][CH3:33].CO.C(OCC)(=O)C>CN(C=O)C>[CH2:32]([O:31][P:30]([CH2:2][C:3]1[CH:8]=[N:7][C:6]([NH:9][C:10](=[O:29])[C:11]2[CH:16]=[C:15]([O:17][CH2:18][CH2:19][C:20]3[CH:24]=[CH:23][S:22][CH:21]=3)[CH:14]=[C:13]([O:25][CH:26]([CH3:28])[CH3:27])[CH:12]=2)=[CH:5][CH:4]=1)(=[O:37])[O:34][CH2:35][CH3:36])[CH3:33]

Participants

5

Reactant 3

HCID 31215Triethyl phosphiteHCID 21584119Ethylacetate methanolHCID 58528875HCID 58528875, compound

Product 1

HCID 58528960HCID 58528960, compoundYield 16.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-(5-Bromomethyl-pyridin-2-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide (0.46 g, 0.97 mmol) was dissolved in DMF (5 mL). Triethyl phosphite (0.51 mL, 2.91 mmol) was added and the reaction mixture was subjected to microwave radiation at 180° C. for 30 minutes. The reaction mixture was concentrated under reduced pressure and partitioned in EtOAc (20 mL) and water (20 mL). The organic layer was rinsed with water (10 mL), and then a saturated sodium chloride solution (10 mL), dried over sodium sulfate, filtered, and concentrated to dark brown oil. After chromatography on silica gel with a gradient from 50-100% ethyl acetate-hexanes to 10% methanol-ethyl acetate, {6-[3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoylamino]-pyridin-3-ylmethyl}-phosphonic acid diethyl ester (86.0 mg, 16.6% yield) was obtained. 1H NMR (300 MHz, DMSO-d6): δ 10.85 (s, 1H), 8.25 (s, 1H), 8.10 (d, J=6.0 Hz, 1H), 7.70 (d, J=6.0 Hz, 1H), 7.45 (d, J=3.0 Hz, 1H), 7.30 (s, 1H), 7.20 (s, 1H), 7.15 (s, 1H), 7.10 (d, J=3.0 Hz, 1H), 6.65 (s, 1H), 4.70 (m, 1H), 4.25 (t, 2H), 3.95 (m, 4H), 3.25 (d, J=12.0 Hz, 2H), 3.05 (t, 2H), 1.25 (s, 6H), 1.15 (m, 6H); LCMS (m/z): 533.2 [C26H33N2O6PS+H]+.

Workup

  1. customat 180° C.
  2. customfor 30 minutes
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. custompartitioned in EtOAc (20 mL)
  5. washThe organic layer was rinsed with water (10 mL)
  6. dry with materiala saturated sodium chloride solution (10 mL), dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to dark brown oil

Sources & evidence

ORD record
ord-d4b1861bd970480e813cf5b42b1b0154
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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