Ammonia → HCID 58466239, compound

HRID 335887Notes

Reaction equation

HRID 335887 reaction equation
[NH3:1].[F:2][C:3]1([F:34])[C:32](=S)[NH:31][C:5]2([C:18]3[CH:17]=[C:16]([O:19][CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:15]=[CH:14][C:13]=3[O:12][C:11]3[C:6]2=[CH:7][C:8]([C:25]2[CH:26]=[N:27][CH:28]=[N:29][CH:30]=2)=[CH:9][CH:10]=3)[CH2:4]1>C1COCC1.[Hg](Cl)Cl>[F:2][C:3]1([F:34])[C:32]([NH2:1])=[N:31][C:5]2([C:18]3[CH:17]=[C:16]([O:19][CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:15]=[CH:14][C:13]=3[O:12][C:11]3[C:6]2=[CH:7][C:8]([C:25]2[CH:26]=[N:27][CH:28]=[N:29][CH:30]=2)=[CH:9][CH:10]=3)[CH2:4]1

Participants

5

Reactant 2

HCID 222Ammonia2×HCID 86658480HCID 86658480, compound

Product 1

HCID 58466239HCID 58466239, compound

Reagents, catalysts & solvents 2

HCID 24085Mercuric ChlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

Ammonia gas was bubbled through a solution of 4,4-difluoro-2′-(neopentyloxy)-7′-(pyrimidin-5-yl)spiro[pyrrolidine-2,9′-xanthene]-5-thione (0.013 g, 0.028 mmol) in THF (0.350 mL) at 55° C. for 2 minutes. Mercury(II) chloride (0.011 g, 0.042 mmol) was added in one portion and ammonia gas was bubbled through for 3 more minutes while heating at 55° C. (THF solution replenished as necessary to maintain a volume of ˜0.2-0.3 mL). The resulting reaction was stirred at 55° C. under nitrogen atmosphere for 14 hours. After cooling, the reaction was partitioned between CH2Cl2 (25 mL) and water (10 mL). The reaction mixture was diluted with a 10:1 mixture of saturated aqueous ammonium chloride/ammonium hydroxide, the layers were separated and the aqueous layer was extracted with CH2Cl2 (3×25 mL). The combined organic extracts were washed with a 10:1 mixture of saturated aqueous ammonium chloride/ammonium hydroxide, water, saturated aqueous sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to provide a residue that was purified by filtering through a pad of silica gel by eluting with 1:10 MeOH 2 M ammonia solution in CH2Cl2 followed by further purification by preparative thin layer chromatography (20:1 CHCl3/MeOH) to provide 4,4-difluoro-2′-(neopentyloxy)-7′-(pyrimidin-5-yl)-3,4-dihydrospiro[pyrrole-2,9′-xanthen]-5-amine as a white solid after triturating with pentane. MS m/z=451.2 [M+H]. This procedure is analogous to that described in Foloppe et al, Tetrahedron Letters, 33, 20, pp. 2803-2804, 1992.

Workup

  1. customwas bubbled through for 3 more minutes
  2. temperatureto maintain a volume of ˜0.2-0.3 mL)
  3. customThe resulting reaction
  4. temperatureAfter cooling
  5. customthe reaction was partitioned between CH2Cl2 (25 mL) and water (10 mL)
  6. additionThe reaction mixture was diluted with a 10:1 mixture of saturated aqueous ammonium chloride/ammonium hydroxide
  7. customthe layers were separated
  8. extractionthe aqueous layer was extracted with CH2Cl2 (3×25 mL)
  9. washThe combined organic extracts were washed with a 10:1 mixture of saturated aqueous ammonium chloride/ammonium hydroxide, water, saturated aqueous sodium chloride
  10. dry with materialdried over sodium sulfate
  11. filtrationThe solution was filtered
  12. concentrationconcentrated in vacuo
  13. customto provide a residue that
  14. customwas purified
  15. filtrationby filtering through a pad of silica gel
  16. washby eluting with 1:10 MeOH 2 M ammonia solution in CH2Cl2
  17. customfollowed by further purification by preparative thin layer chromatography (20:1 CHCl3/MeOH)

Sources & evidence

ORD record
ord-104b95bae8c6476d902fe90772d1bcb6
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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