Ammonia → HCID 58466170, compound

HRID 335889Notes

Reaction equation

HRID 335889 reaction equation
[NH3:1].[F:2][C:3]1([F:34])[C:7](=S)[NH:6][C:5]2([C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=4)[CH:20]=3)[O:15][C:14]3[C:9]2=[CH:10][C:11]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[CH:12][CH:13]=3)[CH2:4]1>C1COCC1>[F:2][C:3]1([F:34])[C:7]([NH2:1])=[N:6][C:5]2([C:21]3[C:16](=[N:17][CH:18]=[C:19]([C:22]4[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=4)[CH:20]=3)[O:15][C:14]3[C:9]2=[CH:10][C:11]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[CH:12][CH:13]=3)[CH2:4]1

Participants

4

Reactant 2

HCID 222Ammonia2×HCID 86658481HCID 86658481, compound

Product 1

HCID 58466170HCID 58466170, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

Ammonia gas was bubbled through a solution of 4′,4′-difluoro-3,7-di(pyridin-3-yl)spiro[chromeno[2,3-b]pyridine-5,2′-pyrrolidine]-5′-thione (0.019 g, 0.041 mmol) in THF (0.691 mL) at 55° C. for 2 minutes. Mercuric chloride (0.019 g, 0.070 mmol) was added in one portion and ammonia gas was bubbled through for 5 more minutes while heating at 55° C. (THF solution replenished as necessary to maintain a volume of ˜0.6 mL). The resulting reaction was stirred at 55° C. under nitrogen atmosphere for 12 hours to completion. After cooling, the reaction was filtered with CH2Cl2, MeOH, and 2:1 mixture of CHCl3/i-PrOH. The filtrate was diluted with a 10:1 mixture of saturated aqueous ammonium chloride/ammonium hydroxide (10 mL), the layers were separated and the aqueous layer was extracted with a 2:1 mixture of CHCl3/i-PrOH (3×20 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 afford a residue that was purified by silica gel chromatography (1:20 MeOH in CH2Cl2, followed by 1:10 2 M ammonia MeOH solution in CH2Cl2) to provide 4′,4′-difluoro-3,7-di(pyridin-3-yl)-3′,4′-dihydrospiro[chromeno[2,3-b]pyridine-5,2′-pyrrol]-5′-amine as an off-white solid after triturating with diethyl ether and pentane. MS m/z=442.0 [M+H].

Workup

  1. customwas bubbled through for 5 more minutes
  2. temperatureto maintain a volume of ˜0.6 mL)
  3. customThe resulting reaction
  4. temperatureAfter cooling
  5. filtrationthe reaction was filtered with CH2Cl2, MeOH, and 2:1 mixture of CHCl3/i-PrOH
  6. additionThe filtrate was diluted with a 10:1 mixture of saturated aqueous ammonium chloride/ammonium hydroxide (10 mL)
  7. customthe layers were separated
  8. extractionthe aqueous layer was extracted with a 2:1 mixture of CHCl3/i-PrOH (3×20 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 afford a residue that
  14. customwas purified by silica gel chromatography (1:20 MeOH in CH2Cl2, followed by 1:10 2 M ammonia MeOH solution in CH2Cl2)

Sources & evidence

ORD record
ord-e0b1497059e740748a14bef9a937719f
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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