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

HRID 1880938Notes

Reaction equation

HRID 1880938 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[C:9]([CH2:14][CH3:15])([F:13])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[H-].[Na+].[CH3:24]I>CC(N(C)C)=O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:24])[C:10](=[O:12])[C:9]([CH2:14][CH3:15])([F:13])[CH2:8][N:7]([CH:16]3[CH2:17][CH2:18][CH2:19][CH2:20]3)[C:6]=2[N:21]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 866358952-Chloro-9-cyclopentyl-7-ethyl-7-fluoro-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one

Product 1

HCID 582149032-Chloro-9-cyclopentyl-7-ethyl-7-fluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-oneYield 80.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of 2-chloro-9-cyclopentyl-7-ethyl-7-fluoro-8,9-dihydro-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one (890 mg, 2.85 mmol) in 10 mL of DMA was added sodium hydride (60% dispersion in mineral oil, 116 mg, 2.9 mmol) at 0° C., followed by the dropwise addition of methyl iodide (0.18 mL, 2.9 mmol). The reaction mixture was warmed up to rt and stirred for 1 h. The whole was poured into ice-water, extracted with ethyl acetate. The organic layer was washed with brine and dried over Na2SO4. The solution was concentrated in vacuo followed by precipitation from ether/EtOA to afford the product (750 mg, 80% yield) as light tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.90 (t, J=7.3 Hz, 3 H) 1.55-1.98 (m, 10 H) 3.28 (s, 3 H) 3.70-3.93 (m, 2 H) 4.74 (t, J=7.9 Hz, 1 H) 8.25 (s, 1 H). [M+H] calc'd for C15H20ClFN4O, 327; found 327.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationThe solution was concentrated in vacuo
  5. customfollowed by precipitation from ether/EtOA

Sources & evidence

ORD record
ord-001083c144bd43bab75a521455be9315
Source dataset
uspto-grants-2012_11
Patent number
US08318727B2

Reaction notes

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