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

HRID 2234520Notes

Reaction equation

HRID 2234520 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:6][C:7](=[O:21])[C:8]3([CH2:20][CH2:19]3)[CH2:9][N:10]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[CH3:22]I.[H-].[Na+]>CC(N(C)C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[C:8]3([CH2:19][CH2:20]3)[CH2:9][N:10]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 579699292'-chloro-9'-cyclohexyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-one2×

Product 1

HCID 579698842'-chloro-9'-cyclohexyl-5'-methyl-8',9'-dihydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepin]-6'(5'H)-oneYield 100%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a stirred solution of 2′-chloro-9′-cyclohexyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 271; 849 mg, 2.767 mmol) in DMA (60 mL) under nitrogen was added methyl iodide (190 μL, 3.044 mmol). The mixture was cooled on an ice/water bath and sodium hydride (60% mineral oil dispersion; 122 mg, 3.044 mmol) added in one portion. The reaction mixture was stirred on the ice/water bath for 1 hour, the cooling bath removed and allowed it to warm to room temperature. After 1.5 hours the solvent was evaporated and the residue treated with an excess of water. This afforded a solid, which was filtered off and washed well with water and then dried by dessication under high vacuum over P2O5 overnight. To yield the title compound as an off-white solid (887 mg, 100%)

Workup

  1. temperatureThe mixture was cooled on an ice/water bath
  2. customthe cooling bath removed
  3. customAfter 1.5 hours the solvent was evaporated
  4. additionthe residue treated with an excess of water
  5. customThis afforded a solid, which
  6. filtrationwas filtered off
  7. washwashed well with water
  8. dry with materialdried by dessication under high vacuum over P2O5 overnight

Sources & evidence

ORD record
ord-598d51459a5040c8914421b14924ec2b
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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