Sodium hydride → HCID 71554399, compound

HRID 1776404Notes

Reaction equation

HRID 1776404 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]2[N:15]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[C:13]([O:23][CH3:24])=[CH:12][N:11]=2)=[N:2]1.[H-].[Na+].Br[CH2:28][C:29]1[C:34]([F:35])=[C:33]([CH3:36])[CH:32]=[CH:31][C:30]=1[Cl:37]>O1CCCC1>[Cl:37][C:30]1[C:29]([CH2:28][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]([C:10]3[N:15]=[C:14]([NH:16][C:17]4[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=4)[C:13]([O:23][CH3:24])=[CH:12][N:11]=3)=[N:2]2)=[C:34]([F:35])[C:33]([CH3:36])=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27736806-Chloro-2-fluoro-3-methylbenzyl bromideHCID 86732418HCID 86732418, compound

Product 1

HCID 71554399HCID 71554399, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

80 mg of 2-(1H-indazol-3-yl)-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine (1-6-1, 0.251 mmol, 1. eq.) were suspended in dry tetrahydrofuran under a nitrogen atmosphere. 30.2 mg of sodium hydride (60% purity) were added and stirred at room temperature for 10 minutes. Then 59.7 mg of 2-(bromomethyl)-1-chloro-3-fluoro-4-methylbenzene were added. The reaction mixture was stirred for 18 hours at room temperature. Then the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1. The phases were separated and the aqueous layer was extracted twice with dichloromethane/isopropanol 4:1. The combined organic layers were washed with brine, dried over a silicone filter and concentrated in vacuo. Preparative HPLC purification provided 29 mg (0.06 mmol, 24.1%) of the analytically pure target compound.

Workup

  1. stirringThe reaction mixture was stirred for 18 hours at room temperature
  2. customThen the mixture was partitioned between half saturated aq. ammonium chloride solution and dichloromethane/isopropanol 4:1
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted twice with dichloromethane/isopropanol 4:1
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over a silicone
  7. filtrationfilter
  8. concentrationconcentrated in vacuo
  9. customPreparative HPLC purification
  10. customprovided 29 mg (0.06 mmol, 24.1%) of the analytically pure target compound

Sources & evidence

ORD record
ord-c19c810e7380487cb1d26dc2c0dfd5c5
Source dataset
uspto-grants-2016_02
Patent number
US09265763B2

Reaction notes

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