Methyl iodide → 2-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

HRID 1880825Notes

Reaction equation

HRID 1880825 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:6][C:7](=[O:20])[C:8]([F:19])([F:18])[CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[H-].[Na+].[CH3:23]I>CC(N(C)C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:23])[C:7](=[O:20])[C:8]([F:18])([F:19])[CH2:9][N:10]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17]3)[C:11]=2[N:12]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 579556112-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-one

Product 1

HCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-oneYield 94%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

2-Chloro-9-cyclopentyl-7,7-difluoro-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (2.4 g, 7.95 mmol) was dissolved in DMA (20 mL) and cooled in an ice bath. Sodium hydride (348 mg of 65% in mineral oil, 8.75 mmol) was added slowly and left to stir for 10 minutes. Methyl iodide (0.546 mL, 8.75 mmol) was then added and then after 10 minutes the solution removed from the bath. After 30 minutes the reaction was deemed complete by LCMS, poured into ice water (300 mL), the solution acidified with 1N HCl, the product filtered off as a yellow solid (2.36 g, 94% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38-2.00 (m, 8 H) 3.34 (s, 3 H) 4.15 (t, J=13.26 Hz, 2 H) 4.80 (q, 1 H) 8.35 (s, 1 H). [M+H] calc'd for C13H15ClF2N4O, 317; found 317.

Workup

  1. temperaturecooled in an ice bath
  2. waitleft
  3. customafter 10 minutes the solution removed from the bath
  4. waitAfter 30 minutes the reaction was deemed complete by LCMS
  5. additionpoured into ice water (300 mL)

Sources & evidence

ORD record
ord-789930244cab4944b89a3423e3a7e9b7
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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