Potassium Phosphate, Tribasic → US10023592, Example 294

HRID 575775Notes

Reaction equation

HRID 575775 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:8][C:7]=2[C:16]2[CH:17]=[C:18](I)[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=2)[CH2:3][CH2:2]1.[CH3:25][CH:26]([N:28]1[CH:32]=[C:31]([OH:33])[CH:30]=[N:29]1)[CH3:27].CC(C)(C(=O)CC(=O)C(C)(C)C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I>[CH:1]1([CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:8][C:7]=2[C:16]2[CH:17]=[C:18]([O:33][C:31]3[CH:30]=[N:29][N:28]([CH:26]([CH3:27])[CH3:25])[CH:32]=3)[C:19](=[O:23])[N:20]([CH3:22])[CH:21]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 130184111-(Propan-2-yl)-1H-pyrazol-4-olHCID 1180215805-[2-(Cyclopropylmethoxy)-5-methylsulfonylphenyl]-3-iodo-1-methylpyridin-2-one

Product 1

HCID 118021336US10023592, Example 294Yield 40%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-3-iodo-1-methylpyridin-2-one (91 mg, 0.2 mmol), 1-propan-2-ylpyrazol-4-ol (45 mg, 0.36 mmol), CuI (4 mg, 10%), 2,2,6,6-tetramethyl-3,5-heptanedione (8 uL, 0.04 mmol) and K3PO4 (85 mg, 0.4 mmol) in DMSO (1 mL) was purged with nitrogen for 10 min, capped, and heated to 110° C. for 13 h. After the mixture was filtered through a short bed of celite, the filtrate was concentrated in vacuo and purified by prep-HPLC to afford the title compound (36 mg, 40%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.18-0.26 (m, 2H) 0.44-0.53 (m, 2H) 1.03-1.10 (m, 1H) 1.37-1.43 (m, 6H) 3.17-3.21 (m, 3H) 3.54-3.61 (m, 3H) 3.87-3.93 (m, 2H) 4.33-4.46 (m, 1H) 7.20-7.25 (m, 1H) 7.25-7.28 (m, 1H) 7.33-7.36 (m, 1H) 7.70-7.74 (m, 1H) 7.76-7.85 (m, 4H). LCMS (M+H)+=458.

Workup

  1. customwas purged with nitrogen for 10 min
  2. customcapped
  3. filtrationAfter the mixture was filtered through a short bed of celite
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-63f48b6cf99e4bd58fc85ef065740836
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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