Tetrahydrofuran → 3-(1-(4-Prop-2-ynyloxymethyl-benzyl)-1H-pyrazol-4-yl)-pyridin-2-ylamine

HRID 1694160Notes

Reaction equation

HRID 1694160 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([NH2:12])=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:3]=[N:2]1.O1CCCC1.[H-].[Na+].Cl[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][O:29][CH2:30][C:31]#[CH:32])=[CH:24][CH:23]=1>O.CN(C)C=O>[CH2:30]([O:29][CH2:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][N:1]2[CH:5]=[C:4]([C:6]3[C:7]([NH2:12])=[N:8][CH:9]=[CH:10][CH:11]=3)[CH:3]=[N:2]2)=[CH:27][CH:26]=1)[C:31]#[CH:32]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 592552251-Chloromethyl-4-prop-2-ynyloxymethyl-benzeneHCID 592552903-(1H-pyrazol-4-yl)-pyridin-2-ylamine

Product 1

HCID 592553613-(1-(4-Prop-2-ynyloxymethyl-benzyl)-1H-pyrazol-4-yl)-pyridin-2-ylamineYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-(1H-pyrazol-4-yl)-pyridin-2-ylamine (30 mg, 0.19 mmol) described in Manufacturing Example 32-1-4 and tetrahydrofuran (1 mL) was added sodium hydride (12 mg, 0.24 mmol, 50% in oil) at 0° C., and then N,N-dimethylformamide (1 mL) was added. The reaction mixture was stirred for 10 minutes at room temperature, after which 1-chloromethyl-4-prop-2-ynyloxymethyl-benzene (47 mg, 0.24 mmol) described in Manufacturing Example 194-1-2 was added to this mixture at 0° C., which was stirred for 2 hours at room temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=4:1) to obtain the title compound (37 mg, 62%).

Workup

  1. additionwas added to this mixture at 0° C.
  2. stirringwhich was stirred for 2 hours at room temperature
  3. extractionwas extracted with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium chloride
  5. concentrationwas concentrated under a reduced pressure
  6. customThe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=4:1)

Sources & evidence

ORD record
ord-66219964ae7f42c885b01b56bb698d11
Source dataset
uspto-grants-2012_04
Patent number
US08158657B2

Reaction notes

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