Methanol → HCID 86652073, compound

HRID 1801711Notes

Reaction equation

HRID 1801711 reaction equation
[F:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[CH2:4][N:5]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]([F:22])=[C:18]([CH:21]=2)[C:19]#[N:20])=[N:12][C:11]2[C:10](=[O:23])[N:9]([CH2:24][CH3:25])[C:8]3=[N:26][C@H:27]([CH:29]([CH3:31])[CH3:30])[CH2:28][N:7]3[C:6]1=2.CO.[NH4+]=[S:40].O>CCOC(C)=O.[Cl-].[Na+].O>[F:1][C:2]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:3]=1[CH2:4][N:5]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]([F:22])=[C:18]([CH:21]=2)[C:19](=[S:40])[NH2:20])=[N:12][C:11]2[C:10](=[O:23])[N:9]([CH2:24][CH3:25])[C:8]3=[N:26][C@H:27]([CH:29]([CH3:31])[CH3:30])[CH2:28][N:7]3[C:6]1=2

Participants

6

Reactant 3

HCID 887MethanolHCID 962WaterHCID 58192450HCID 58192450, compound

Product 1

HCID 86652073HCID 86652073, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
85 °C

Procedure

A 10 mL microwave vial was charged with (R)-5-(1-(2,4-difluorobenzyl)-5-ethyl-7-isopropyl-4-oxo-4,5,7,8-tetrahydro-1H-imidazo[2,1-b]purin-2-yl)-2-fluorobenzonitrile (50) (275 mg, 0.558 mmol), MeOH (5 mL), and ammonium sulfide solution in water (20 wt %, 600 μL, 1.67 mmol). The reaction mixture was stirred in a microwave at 85° C. for 15 minutes, cooled to room temperature and concentrated in vacuo. The residue obtained was diluted with EtOAc (200 mL) and brine (250 mL) and the layers separated. The aqueous phase was extracted with EtOAc (200 mL) and the combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified using CombiFlash chromatography (silica gel, 96:4, CH2Cl2/MeOH) to provide (R)-5-(1-(2,4-difluorobenzyl)-5-ethyl-7-isopropyl-4-oxo-4,5,7,8-tetrahydro-1H-imidazo[2,1-b]purin-2-yl)-2-fluorobenzothioamide (118 mg, 40%) as a yellow solid.

Workup

  1. temperaturecooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue obtained
  4. customthe layers separated
  5. extractionThe aqueous phase was extracted with EtOAc (200 mL)
  6. dry with materialthe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-be8efa21c9eb4b08a1b3441c02253c0f
Source dataset
uspto-grants-2013_01
Patent number
US08349858B2

Reaction notes

Loading…