Acetic Acid → HCID 59312783, compound

HRID 1931550Notes

Reaction equation

HRID 1931550 reaction equation
[C:1](O)(=O)C.C=O.O.[C:8]([BH3-])#[N:9].[Na+].C1COCC1.[NH2:17][C:18]([C:20]1[N:24]([C@@H:25]2[CH2:56][C@:29]34[C:33]5[C@H:42]([CH2:43][CH2:44][C@H:28]3[C@@:27]([CH3:57])([CH2:32][O:31][CH2:30]4)[C@H:26]2[O:58][CH2:59][C@@:60](N)([CH3:64])[CH:61]([CH3:63])[CH3:62])[C@:41]2([CH3:45])[C@:36]([CH3:55])([C@H:37]([C:52]([OH:54])=[O:53])[C@:38]([C@H:47]([CH3:51])[CH:48]([CH3:50])[CH3:49])([CH3:46])[CH2:39][CH2:40]2)[CH2:35][CH:34]=5)[N:23]=[CH:22][N:21]=1)=[O:19]>CO>[NH2:17][C:18]([C:20]1[N:24]([C@@H:25]2[CH2:56][C@:29]34[C:33]5[C@H:42]([CH2:43][CH2:44][C@H:28]3[C@@:27]([CH3:57])([CH2:32][O:31][CH2:30]4)[C@H:26]2[O:58][CH2:59][C@@:60]([N:9]([CH3:8])[CH3:1])([CH3:64])[CH:61]([CH3:63])[CH3:62])[C@:41]2([CH3:45])[C@:36]([CH3:55])([C@H:37]([C:52]([OH:54])=[O:53])[C@:38]([C@H:47]([CH3:51])[CH:48]([CH3:50])[CH3:49])([CH3:46])[CH2:39][CH2:40]2)[CH2:35][CH:34]=5)[N:23]=[CH:22][N:21]=1)=[O:19]

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 712FormaldehydeHCID 962WaterHCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 59312600HCID 59312600, compound

Product 1

HCID 59312783HCID 59312783, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetic acid (2 μl, 0.035 mmol), formaldehyde 37% in water (5.4 μl, 0.073 mmol), and sodium cyanoborohydride 1.0 M in THF (67 μl, 0.067 mmol) were added to a stirred hazy solution of (1S,4aR,6aS,7R,8R,10aR,10bR,12aR,14R,15R)-14-[5-(aminocarbonyl)-1H-1,2,4-triazol-1-yl]-15-[[(2R)-2-amino-2,3-dimethylbutyl]oxy]-8-[(1R)-1,2-dimethylpropyl]-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 41, 13.3 mg, 0.017 mmol) in methanol (0.33 ml). The reaction mixture was a hazy solution. After 6 hr, LCMS showed complete consumption of starting material. The reaction mixture was diluted with methanol, the solvent was evaporated under reduced pressure, and the resulting residue was placed under high vacuum. The residue was dissolved in methanol and purified using a single HPLC run on a 19×150 mm Sunfire Prep C18 OBD 10 μm column by eluting with acetonitrile/water+0.1% TFA. The total flow rate was 15 ml/min and the HPLC method employed a 12 minute 20%-100% acetonitrile/water gradient followed by a 7 minute acetonitrile flush. The product HPLC fractions were combined and the solvent was evaporated under reduced pressure to give the title compound as a colorless residue.

Workup

  1. customconsumption of starting material
  2. additionThe reaction mixture was diluted with methanol
  3. customthe solvent was evaporated under reduced pressure
  4. dissolutionThe residue was dissolved in methanol
  5. custompurified
  6. washby eluting with acetonitrile/water+0.1% TFA
  7. waitThe total flow rate was 15 ml/min and the HPLC method employed a 12 minute
  8. wait20%-100% acetonitrile/water gradient followed by a 7 minute
  9. customacetonitrile flush
  10. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-cde1558b1d6e426d979f3796d6ae0a8a
Source dataset
uspto-grants-2012_05
Patent number
US08188085B2

Reaction notes

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