Sodium hydride → HCID 89570389, compound

HRID 530106Notes

Reaction equation

HRID 530106 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@@H:6]([CH3:21])[NH:5][C:4]=2[N:3]=1.[CH:22]1([CH2:26]Br)[CH2:25][CH2:24][CH2:23]1.[H-].[Na+]>CN(C=O)C.O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@@H:6]([CH3:21])[N:5]([CH2:26][CH:22]3[CH2:25][CH2:24][CH2:23]3)[C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2734658(Bromomethyl)cyclobutaneHCID 89570386HCID 89570386, compound

Product 1

HCID 89570389HCID 89570389, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-[(7R)-2-chloro-7-methyl-6-oxo-7,8-dihydropteridin-5(6H)-yl]benzonitrile (120 mg, 0.4 mmol) in anhydrous DMF (3 ml) was added cyclobutyl methyl bromide (119 mg, 0.8 mmol) at 0° C. under nitrogen. To the resulting solution was added sodium hydride (32 mg of 60% dispersion in oil, 0.8 mmol) at 0° C. The reaction was then allowed to warm up to rt in 20 min and then heated at 50° C. for 3 h. The reaction mixture was diluted with water (20 ml) and extracted with ethyl acetate (30 mL×3). The organic layers were combined, dried (Na2SO4) and evaporated to give a crude residue, which was then purified by silica gel flash chromatography (eluent: 2% methanol in dichloromethane) to give desired product (Yield: 41%). 1HNMR (300 MHz, CDCl3) δ 1.50 (d, J=6.9 Hz, 3H), 1.78-1.94 (m, 4H), 1.96-2.21 (m, 2H), 2.68-2.87 (m, 1H), 3.17 (q, J=6.9 Hz, 1H), 4.22-4.36 (m, 2H), 7.10 (s, 1H), 7.50 (d, J=7.8 Hz, 1H), 7.58 (s, 1H), 7.66-7.78 (m, 1H) and 7.79-7.81 (m, 1H).

Workup

  1. temperatureheated at 50° C. for 3 h
  2. extractionextracted with ethyl acetate (30 mL×3)
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customto give a crude residue, which
  6. customwas then purified by silica gel flash chromatography (eluent: 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9095bbbda50c42629d5113ab3008f206
Source dataset
uspto-grants-2016_05
Patent number
US09351974B2

Reaction notes

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