Water → HCID 12147082, compound

HRID 2415699Notes

Reaction equation

HRID 2415699 reaction equation
[OH-].[Na+].[C:3]1([OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:10][O:11][C:12]([CH:14]1[CH2:19][CH2:18][CH2:17][N:16]2[C:20](=[O:40])[C:21]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)=[C:22]([C:23]3[CH:28]=[CH:27][N:26]=[C:25](S(C)(=O)=O)[N:24]=3)[N:15]12)=[O:13].O>C1COCC1>[CH3:10][O:11][C:12]([C@@H:14]1[CH2:19][CH2:18][CH2:17][N:16]2[C:20](=[O:40])[C:21]([C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)=[C:22]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([O:9][C:3]4[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=4)[N:24]=3)[N:15]12)=[O:13]

Participants

6

Reactant 4

HCID 962WaterHCID 996PhenolHCID 14798Sodium HydroxideHCID 23526875HCID 23526875, compound

Product 1

HCID 12147082HCID 12147082, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

NaOH (0.112 g, 2.8 mmol) is added to a solution of phenol (0.316 g, 3.36 mmol) in THF (100 mL). 2-(4-Fluorophenyl)-3-(2-methanesulfonylpyrimidin-4-yl)-1-oxo-5,6,7,8-tetrahydro-1H-pyrazolo[1,2-a]pyridazine-5-carboxylic acid methyl ester, 32, (0.5 g) is dissolved in THF (50 mL) and added dropwise to the solution over 5 minutes. The resulting mixture is stirred at room temperature for 8 hours after which water (20 mL) is added. The solution is extracted with ethyl acetate (100 mL the organic layer washed with brine (50 mL) and concentrated in vacuo to afford 0.278 g (54% yield) of the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 1.75 (m, 2 H), 1.97 (m 1 H), 2.42 (d, J=12.8 Hz, 1 H), 3.27 (m, 1 H), 3.27 (m, 1 H), 3.6 (s, 3 H), 4.5 (br d, J=12.8 Hz, 1 H), 5.25 (m, 1 H), 6.87 (d, J=5.7 Hz, 1 H), 7.05 (m, 2H), 7.23 (m, 2 H), 7.35 (m, 3 H), 7.52 (m, 2 H), 8.42 (d, J=5.7 Hz, 1 H): exact mass calc. for C25H21FN4O4 460.46, MS-ESI (M+1) 461.

Workup

  1. additionadded dropwise to the solution over 5 minutes
  2. additionis added
  3. extractionThe solution is extracted with ethyl acetate (100 mL the organic layer
  4. washwashed with brine (50 mL)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fd6ac40d6fc3484f919aea6b45d0bfde
Source dataset
uspto-grants-2004_11
Patent number
US06821971B2

Reaction notes

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