Hydrazine hydrate (1:1) → HCID 58504813, compound

HRID 2367512Notes

Reaction equation

HRID 2367512 reaction equation
F[C:2]1[CH:9]=[C:8]([C:10]2[CH:15]=[C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][C@H:17]3[CH:22]([CH3:24])[CH3:23])[N:13]=[C:12]([NH:25][CH3:26])[N:11]=2)[CH:7]=[C:6]([S:27][CH3:28])[C:3]=1[C:4]#[N:5].O.[NH2:30][NH2:31]>C(O)C>[CH3:26][NH:25][C:12]1[N:11]=[C:10]([C:8]2[CH:9]=[C:2]3[C:3]([C:4]([NH2:5])=[N:30][NH:31]3)=[C:6]([S:27][CH3:28])[CH:7]=2)[CH:15]=[C:14]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][C@H:17]2[CH:22]([CH3:23])[CH3:24])[N:13]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504660HCID 58504660, compound

Product 1

HCID 58504813HCID 58504813, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 2-fluoro-4-{2-(methylamino)-6-[(3R)-3-(1-methylethyl)-4-morpholinyl]-4-pyrimidinyl}-6-(methylthio)benzonitrile (350 mg, 0.87 mmol) in ethanol (10 mL) was added hydrazine monohydrate (2.5 mL) in one portion. The resulting suspension was heated in an oil bath to 100° C. under a reflux condenser for 20 hours. LCMS showed complete conversion. The mixture was filtered through celite, and the filtrate was concentrated in vacuo. The residue was taken up in water (30 mL) and sonicated briefly. The resulting suspension was filtered. The collected solids underwent purification by silica gel column chromatography using gradient elution of 1% A in CHCl3 to 100% A (where A was a mixture of 800/80/3200 CH3OH/NH4OH/CHCl3). After removal of eluant solvents, the residue was redissolved in CHCl3, filtered, and concentrated in vacuo. The residue was taken up in water (15 mL) as a suspension. The solids formed were collected by filtration and dryed under vacuum at room temperature over P2O5 for 20 hours. These solids were washed with hexane (3×3 mL). Further drying under vacuum at 65° C. for 20 hours gave the title compound (282 mg) as a cream-colored solid. LC-MS (ES) m/z=414 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 0.89 (d, J=6.8 Hz, 3H), 1.11 (d, J=6.6 Hz, 3H), 2.45-2.55 (m, 1H), 2.65 (s, 3H), 2.96 (s, 3H), 3.25-3.35 (m, 1H), 3.53-3.61 (m, 2H), 3.94 (dd, J=11.2, 3.4 Hz, 1H), 4.11 (d, J=11.9 Hz, 1H), 6.40 (s, 1H), 7.40 (s, 1H), 7.62 (s, 1H).

Workup

  1. filtrationThe mixture was filtered through celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. customsonicated briefly
  4. filtrationThe resulting suspension was filtered
  5. customThe collected solids underwent purification by silica gel column chromatography
  6. washelution of 1% A in CHCl3 to 100% A (where
  7. additiona mixture of 800/80/3200 CH3OH/NH4OH/CHCl3)
  8. customAfter removal of eluant solvents
  9. dissolutionthe residue was redissolved in CHCl3
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe solids formed
  13. filtrationwere collected by filtration
  14. washThese solids were washed with hexane (3×3 mL)
  15. customFurther drying under vacuum at 65° C. for 20 hours

Sources & evidence

ORD record
ord-e0be910164874a21b67906ce0c756f92
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…