Sodium hydride → HCID 25056868, compound

HRID 2387481Notes

Reaction equation

HRID 2387481 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH2:17][CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[N:12]=[CH:11]3)[C:4](=[O:24])[CH:3]=1.[H-].[Na+].[F:27][C:28]([F:38])([F:37])[C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Br)=[CH:31][CH:30]=1>C1COCC1>[N:19]1([CH2:18][CH2:17][N:13]2[C:14]3[C:10](=[CH:9][C:8]([N:5]4[CH:6]=[CH:7][C:2]([O:1][CH2:33][C:32]5[CH:31]=[CH:30][C:29]([C:28]([F:27])([F:37])[F:38])=[CH:36][CH:35]=5)=[CH:3][C:4]4=[O:24])=[CH:16][CH:15]=3)[CH:11]=[N:12]2)[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 57625508HCID 57625508, compound

Product 1

HCID 25056868HCID 25056868, compoundYield 13.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 4-hydroxy-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one (100 mg, 0.308 mmol) in THF was added NaH (25 mg, 0.62 mmol) followed by 4-(trifluoromethyl)benzyl bromide (88 mg, 0.37 mmol). After heating at 65° C. overnight, the reaction mixture was cooled down, filtered through a thin layer of Celite, washed with CH2Cl2, and the filtrate was concentrated. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 90:10) gave 1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)benzyloxy)pyridine-2(1H)-one (20 mg, 13%) as a white solid. According to the procedure of Example 1, the HCl salt was made to give the title compound as a white solid: 1H NMR (500 MHz, DMSO-d6) δ 9.65 (s, 1H), 8.12 (m, 1H), 7.80-7.67 (m, 6H), 7.62 (d, J=7.5 Hz, 1H), 7.34 (m, 1H), 6.13 (dd, J=7.5, 2.5 Hz, 1H), 5.98 (d, J=2.5 Hz, 1H), 5.27 (s, 2H), 4.58-4.54 (m, 2H), 2.89 (m, 2H), 2.52-2.42 (m, 4H), 1.73-1.64 (m, 4H); ESI MS m/z 483 [M+H]+.

Workup

  1. temperaturethe reaction mixture was cooled down
  2. filtrationfiltered through a thin layer of Celite
  3. washwashed with CH2Cl2
  4. concentrationthe filtrate was concentrated
  5. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 90:10)

Sources & evidence

ORD record
ord-a2ce511edc6b4c3d960bb9ca959f00ec
Source dataset
uspto-grants-2012_09
Patent number
US08268868B2

Reaction notes

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