Sodium hydride → 3-[2-(4,6-Dichloro-pyrimidin-5-ylamino)-pyrimidin-4-yl]-2-(4-fluoro-phenyl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

HRID 22697

Reaction equation

HRID 22697 reaction equation
[NH2:1][C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[N:6][C:7]=1[Cl:8].[H-].[Na+].[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:26](=[O:27])[N:22]3[CH2:23][CH2:24][CH2:25][N:21]3[C:20]=2[C:28]2[CH:33]=[CH:32][N:31]=[C:30](S(C)(=O)=O)[N:29]=2)=[CH:15][CH:14]=1>C1COCC1.[NH4+].[Cl-]>[Cl:9][C:3]1[C:2]([NH:1][C:30]2[N:29]=[C:28]([C:20]3[N:21]4[CH2:25][CH2:24][CH2:23][N:22]4[C:26](=[O:27])[C:19]=3[C:16]3[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=3)[CH:33]=[CH:32][N:31]=2)=[C:7]([Cl:8])[N:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 794345-Amino-4,6-dichloropyrimidineHCID 129914052-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Product 1

HCID 99815613-[2-(4,6-Dichloro-pyrimidin-5-ylamino)-pyrimidin-4-yl]-2-(4-fluoro-phenyl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 5-amino-4,6-dichloropyrimidine (219 mg, 1.34 mmol) in THF (4 mL) is added NaH (0.07 g, 1.00 mmol). After stirring the mixture for 5 min at room temperature, 2-(4-fluorophenyl)-3-(2-methanesulfonyl-pyrimidin-4-yl)-6,7-dihydro-5H-pyrazolo[1,2-a]pyrazol-1-one, 5, (0.25 g, 0.67 mmol) is added to the reaction mixture. The reaction mixture is heated to reflux and stirred for 1 h. The mixture is diluted with aqueous saturated NH4Cl and extracted with twice with chloroform. The organic layers are combined, dried over MgSO4, and concentrated in vacuo to afford the crude product that is purified over silica (5% MeOH/chloroform) to provide the desired product as a yellow solid. 1H NMR (300 MHz, CDCl3) □ 8.77 (s, 1H), 8.35 (d, J=5.1 Hz, 1H), 7.35 (dd, J=9.0, 5.1 Hz, 1H), 7.10 (dd, J=8.7, 8.7 Hz, 2H), 6.71 (d, J=5.1 Hz, 1H), 4.25 (t, J=6.9 Hz, 2H), 4.12 (t, J=6.9 Hz, 2H), 2.74 (dddd, J=6.9, 6.9, 6.9, 6.9 Hz, 2H). ESI+ MS m/z (rel intensity) 458.1 (100, M++H). This compound corresponds to analog 441 from Table X.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux
  3. stirringstirred for 1 h
  4. extractionextracted with twice with chloroform
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto afford the crude product that
  8. customis purified over silica (5% MeOH/chloroform)

Sources & evidence

ORD record
ord-1fd63287c7cb4867850a59a44a8c6f0b
Source dataset
uspto-grants-2005_02
Patent number
US06849627B2

Linked notes

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