Methanol → {4-[3-Isopropoxy-5-(thiazol-2-ylcarbamoyl)phenoxy]phenyl}phosphonic acid monomethyl ester

HRID 1431027Notes

Reaction equation

HRID 1431027 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH:19]=[C:20]([C:22](=[O:29])[NH:23][C:24]2[S:25][CH:26]=[CH:27][N:28]=2)[CH:21]=1)[O:8][C:9]1[CH:14]=[CH:13][C:12]([P:15](=[O:18])([OH:17])[OH:16])=[CH:11][CH:10]=1)([CH3:3])[CH3:2].CO.[CH3:32]CN=C=NCCCN(C)C.[OH-].[Na+]>CN(C=O)C.N1C=CC=CC=1.O>[CH3:32][O:18][P:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][C:7]2[CH:19]=[C:20]([C:22](=[O:29])[NH:23][C:24]3[S:25][CH:26]=[CH:27][N:28]=3)[CH:21]=[C:5]([O:4][CH:1]([CH3:3])[CH3:2])[CH:6]=2)=[CH:10][CH:11]=1)(=[O:17])[OH:16]

Participants

8

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 58529006{4-[3-Isopropoxy-5-(thiazol-2-ylcarbamoyl)-phenoxy]-phenyl}-phosphonic acid

Product 1

HCID 58529062{4-[3-Isopropoxy-5-(thiazol-2-ylcarbamoyl)phenoxy]phenyl}phosphonic acid monomethyl esterYield 25%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of {4-[3-isopropoxy-5-(thiazol-2-ylcarbamoyl)-phenoxy]-phenyl}-phosphonic acid (Example 3) (100 mg, 0.225 mmol) in DMF (2 mL) and pyridine (300 μL) was added methanol (91 μL, 2.25 mmol) and EDCI (47 mg, 0.247 mmol). The resulting mixture was subjected to microwave heating at 130° C. for 5 min. Then NaOH (2 mL) was added and the resulting mixture was stirred at rt for 10 min. The residue was partitioned between EtOAc and H2O. The aqueous layer was acidified with HCl (6N) to pH 2 and extracted into EtOAc. The organic layer was washed with brine (2×), dried and concentrated to give an oil. Water was added (10 mL) until a precipitate formed which was filtered and dried to afford 25 mg (25%) of {4-[3-isopropoxy-5-(thiazol-2-ylcarbamoyl)phenoxy]phenyl}phosphonic acid monomethyl ester. 1H NMR (500 MHz, DMSO-d6): δ 7.71 (dd, J=12, 9 Hz, 2H), 7.53 (m, 2H), 7.32 (m, 2H), 7.15 (dd, J=9, 3 Hz, 2H), 6.89 (t, J=3 Hz, 1H), 4.76 (m, 1H), 3.52 (d, J=11 Hz, 3H), 1.30 (d, J=6 Hz, 6H); LCMS m/z=449.6 [C20H21N2O6PS+H]+; Anal. Calcd. for (C20H21N2O6PS+0.5H2O): C, 52.51; H, 4.85; N, 6.12. Found: C, 52.54; H, 4.93; N, 6.15.

Workup

  1. customThe residue was partitioned between EtOAc and H2O
  2. extractionextracted into EtOAc
  3. washThe organic layer was washed with brine (2×)
  4. customdried
  5. concentrationconcentrated
  6. customto give an oil
  7. customformed which
  8. filtrationwas filtered
  9. customdried

Sources & evidence

ORD record
ord-7053b8cafb2649beac8e7eccb966a9fa
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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