Ammonium Hydroxide → HCID 59312597, compound

HRID 1931553Notes

Reaction equation

HRID 1931553 reaction equation
[OH-:1].[NH4+:2].[NH2:3][C@:4]([CH3:60])([C:56]([CH3:59])([CH3:58])[CH3:57])[CH2:5][O:6][C@@H:7]1[C@@:14]2([CH3:39])[C@@H:15]3[CH2:16][CH2:17][C@H:18]4[C:27]([C@@:10]3([CH2:11][O:12][CH2:13]2)[CH2:9][C@H:8]1[N:40]1[C:44]([C:45]2[CH:50]=[CH:49][N:48]=[C:47]([C:51](OCC)=O)[CH:46]=2)=[N:43][CH:42]=[N:41]1)=[CH:26][CH2:25][C@:24]1([CH3:28])[C@:19]4([CH3:38])[CH2:20][CH2:21][C@@:22]([C@H:33]([CH3:37])[CH:34]([CH3:36])[CH3:35])([CH3:32])[C@H:23]1[C:29]([OH:31])=[O:30]>O1CCOCC1.CO>[NH2:2][C:51]([C:47]1[CH:46]=[C:45]([C:44]2[N:40]([C@@H:8]3[CH2:9][C@:10]45[C:27]6[C@H:18]([CH2:17][CH2:16][C@H:15]4[C@@:14]([CH3:39])([CH2:13][O:12][CH2:11]5)[C@H:7]3[O:6][CH2:5][C@@:4]([NH2:3])([CH3:60])[C:56]([CH3:57])([CH3:59])[CH3:58])[C@:19]3([CH3:38])[C@:24]([CH3:28])([C@H:23]([C:29]([OH:31])=[O:30])[C@:22]([C@H:33]([CH3:37])[CH:34]([CH3:36])[CH3:35])([CH3:32])[CH2:21][CH2:20]3)[CH2:25][CH:26]=6)[N:41]=[CH:42][N:43]=2)[CH:50]=[CH:49][N:48]=1)=[O:1]

Participants

5

Reactant 2

HCID 14923Ammonium Hydroxide3×HCID 59312648HCID 59312648, compound

Product 1

HCID 59312597HCID 59312597, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

Concentrated ammonium hydroxide (0.15 ml, 1.079 mmol) was added to a stirred solution of (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-15-[[(2R)-2-amino-2,3,3-trimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-14-[5-[2-(ethoxycarbonyl)-4-pyridinyl]-1H-1,2,4-triazol-1-yl]-1,6,6a,7,8,9,10,10a,10b,11,12,12a-dodecahydro-1,6a,8,10a-tetramethyl-4H-1,4a-propano-2H-phenanthro[1,2-c]pyran-7-carboxylic acid (Example 171, 38.1, 0.042 mmol) in 1,4-dioxane (0.42 ml). A white precipitate formed about a minute or two after the addition of ammonium hydroxide. The reaction mixture was stirred at room temperature. After 20 hours, additional 1,4-dioxane (0.15 ml) and concentrated ammonium hydroxide (0.05 ml, 0.360 mmol) were added to the reaction mixture. After 26 hours, the reaction mixture had become a colorless solution. After 44 hours, LCMS and 1H NMR showed the reaction to be complete. The reaction mixture was evaporated under reduced pressure to give a colorless residue. The residue was dissolved in methanol and purified using a single HPLC run on a 30×150 mm Sunfire Prep C18 OBD 10 μm column by eluting with acetonitrile/water+0.1% TFA. The total flow rate was 20 ml/min and the HPLC method employed a 17 minute 20%-100% acetonitrile/water gradient followed by a 2 minute acetonitrile flush. The product fractions were combined, the solvent was evaporated under reduced pressure, and the residue was lyophilized from acetonitrile and water to give the title compound (29.9 mg) as a white solid.

Workup

  1. customA white precipitate formed about a minute or two
  2. waitAfter 26 hours
  3. waitAfter 44 hours
  4. customthe reaction
  5. customThe reaction mixture was evaporated under reduced pressure
  6. customto give a colorless residue
  7. custompurified
  8. washby eluting with acetonitrile/water+0.1% TFA
  9. waitThe total flow rate was 20 ml/min and the HPLC method employed a 17 minute
  10. wait20%-100% acetonitrile/water gradient followed by a 2 minute
  11. customacetonitrile flush
  12. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-fd80796b76754d07ab218cd735f7362c
Source dataset
uspto-grants-2012_05
Patent number
US08188085B2

Reaction notes

Loading…