Phenol → HCID 12147078, compound

HRID 2415694Notes

Reaction equation

HRID 2415694 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][N:7]2[C:11]([C:22]3[N:23](S(C)(=O)=O)[CH2:24][N:25]=[CH:26][CH:27]=3)=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:13](=[O:14])[N:6]12)=[O:4].[C:32]1([OH:38])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[H-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]([CH:5]1[CH2:10][CH2:9][CH2:8][N:7]2[C:11]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([O:38][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[N:23]=3)=[C:12]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:13](=[O:14])[N:6]12)=[O:4]

Participants

5

Reactant 3

HCID 996PhenolHCID 24758Sodium hydrideHCID 69702952HCID 69702952, compound

Product 1

HCID 12147078HCID 12147078, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4fluorophenyl)-1-(3-methanesulfonyl-pyrimidin-4-yl)-3-oxo-5,6,7,8-tetrahydro-3H-pyrazolo[1,2-a]pyridazine-5-carboxylic acid methyl ester, 21, (0.033 g, 0.074 mmol) in THF (3 mL) is added phenol and NaH (0.009 g, 0.22 mmol). The reaction mixture is stirred at room temperature for 1 hour. The reaction is quenched by the addition of 1 N HCl (20 mL) and the solution is extracted with ethyl acetate (3×25 mL). The organic phases are combined, washed with brine, dried, and concentrated in vacuo to afford the crude product which is purified over silica (hexanes/ethyl acetate 1:3) to afford 0.012 g (35% yield) of the desired product as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.64 (d, J=4.6 Hz 1 H), 7.59-7.63 (m, 2 H), 7.40-7.45 (m, 3 H), 7.28-7.30 (m, 1 H), 7.18 (d, J=8.4 Hz, 2 H), 7.03-7.08 (m, 2 H), 4.50-4.56 (m, 1 H), 3.99-4.04 (m, 1 H), 3.86 (s, 1 H), 3.01-3.10 (m, 1 H), 2.33-2.41 (m, 1 H), 1.86 (brs, 2 H), 1.64 (brs, 3 H); ESI/MS: 461 (M+H).

Workup

  1. customThe reaction is quenched by the addition of 1 N HCl (20 mL)
  2. extractionthe solution is extracted with ethyl acetate (3×25 mL)
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product which
  7. customis purified over silica (hexanes/ethyl acetate 1:3)

Sources & evidence

ORD record
ord-c53e5aa97a274841bd116d8be1189fa7
Source dataset
uspto-grants-2004_11
Patent number
US06821971B2

Reaction notes

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