Methyl iodide → 2'-chloro-9'-isopropyl-5'-methyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-one

HRID 2234475Notes

Reaction equation

HRID 2234475 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:6][C:7](=[O:18])[C:8]3([CH2:17][CH2:16]3)[CH2:9][N:10]([CH:13]([CH3:15])[CH3:14])[C:11]=2[N:12]=1.[CH3:19]I.[H-].[Na+]>CC(N(C)C)=O.C(Cl)Cl>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:19])[C:7](=[O:18])[C:8]3([CH2:16][CH2:17]3)[CH2:9][N:10]([CH:13]([CH3:15])[CH3:14])[C:11]=2[N:12]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 866175872'-chloro-9'-isopropyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-one2×

Product 1

HCID 866175592'-chloro-9'-isopropyl-5'-methyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-oneYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 2′-chloro-9′-isopropyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 209; 5.055 g, 19 mmol) in DMA (300 mL) was added methyl iodide (1.305 mL, 20.9 mmol), followed by sodium hydride (60% mineral oil dispersion; 814 mg, 20.33 mmol). The mixture was stirred at room temperature for 30 minutes. The DMA was removed in vacuo, then water (50 mL) was added. The product precipitated as a sticky gum, which turned into a solid on sonication. The solid was collected by filtration to give a brown powder. This material was dissolved in DCM and dried over sodium sulfate, then purified by column chromatography, eluting with 25% ethyl acetate in hexane, to yield the title compound as a white solid (3.73 g, 70%)

Workup

  1. customThe DMA was removed in vacuo
  2. additionwater (50 mL) was added
  3. customThe product precipitated as a sticky gum, which
  4. customturned into a solid on sonication
  5. filtrationThe solid was collected by filtration
  6. customto give a brown powder
  7. dry with materialdried over sodium sulfate
  8. custompurified by column chromatography
  9. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-22475971552642b0bc68e649ed03699a
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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