Ammonia → HCID 11741227, compound

HRID 1785404Notes

Reaction equation

HRID 1785404 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[C:14]([CH:16]([OH:21])[CH2:17][N:18]([CH3:20])[CH3:19])[CH:13]=[CH:12][N:11]3[C:22]=2[C:23]2[CH:28]=[CH:27][N:26]=[C:25](S(C)(=O)=O)[N:24]=2)=[CH:4][CH:3]=1.[NH3:33]>O1CCCC1>[NH2:33][C:25]1[N:24]=[C:23]([C:22]2[N:11]3[CH:12]=[CH:13][C:14]([CH:16]([OH:21])[CH2:17][N:18]([CH3:20])[CH3:19])=[CH:15][C:10]3=[N:9][C:8]=2[C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH:28]=[CH:27][N:26]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 57595178HCID 57595178, compound

Product 1

HCID 11741227HCID 11741227, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A pressure bottle containing sulfone 43 (320 mg, 0.703 mmol) was charged with tetrahydrofuran (40 mL), then chilled to <−40° C. in a dry ice/isopropanol bath. Ammonia gas (5.3 g, 0.31 mol) was then bubbled into the reaction. The pressure bottle was then sealed, and the reaction was allowed to warm to room temperature while stirring for 12 hours. The pressure was then released, and the reaction was concentrated under reduced pressure, dissolved in a minimum volume of CH2Cl2, then loaded onto a 40 g Isco RediSep normal phase silica cartridge, and purified on an Isco OptiX10 CombiFlash instrument using a gradient that started at 100% methylene chloride and ended at 90% methylene chloride, 9% methanol, 1% concentrated ammonium hydroxide. Fractions containing desired product were pooled and concentrated under reduced pressure. Yield of 44: 158 mg (57%). 1H NMR (400 MHz, DMSO-d6) δ 2.21 (s, 6H), 2.49 (m, 2H), 4.77 (m, 1H), 5.38 (m, 1H), 6.31 (d, J=5.4 Hz, 1H), 6.83 (bs, 2H), 7.04 (dd, J=7.2, 1.6 Hz, 1H), 7.28 (t, J=8.8 Hz, 2H), 7.60 (s, 1), 7.65 (m, 2H), 8.10 (d, J=5.4 Hz, 1H), 9.48 (d, J=7.2 Hz, 1H). MS (ESI+) 393.2.

Workup

  1. temperaturechilled to <−40° C. in a dry ice/isopropanol bath
  2. customThe pressure bottle was then sealed
  3. concentrationthe reaction was concentrated under reduced pressure
  4. dissolutiondissolved in a minimum volume of CH2Cl2
  5. custompurified on an Isco OptiX10 CombiFlash instrument
  6. additionFractions containing desired product
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1375763e9574418eb3c62ab805798e6d
Source dataset
uspto-grants-2009_03
Patent number
US07504501B2

Reaction notes

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