Water → HCID 58438498, compound

HRID 1913481Notes

Reaction equation

HRID 1913481 reaction equation
O.OO.N[C:5]([NH2:7])=[O:6].[OH-].[Na+].[CH3:10][O:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][C:19]([N:21]2[CH2:46][CH2:45][C:24]3([CH2:27][N:26]([C@H:28]4[C:36]5[C:31](=[CH:32][C:33]([C:37]6[CH:44]=[CH:43][C:40](C#N)=[CH:39][N:38]=6)=[CH:34][CH:35]=5)[CH2:30][CH2:29]4)[CH2:25]3)[CH2:23][CH2:22]2)=[O:20])=[N:16][CH:17]=1>CCO>[CH3:10][O:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:18][C:19]([N:21]2[CH2:22][CH2:23][C:24]3([CH2:27][N:26]([C@H:28]4[C:36]5[C:31](=[CH:32][C:33]([C:37]6[CH:44]=[CH:43][C:40]([C:5]([NH2:7])=[O:6])=[CH:39][N:38]=6)=[CH:34][CH:35]=5)[CH2:30][CH2:29]4)[CH2:25]3)[CH2:45][CH2:46]2)=[O:20])=[N:16][CH:17]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 31294Carbamide PeroxideHCID 58438520HCID 58438520, compound

Product 1

HCID 58438498HCID 58438498, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of water (30 mL) and urea hydrogen peroxide (165 mg, 1.70 mmol) was added sodium hydroxide (39.8 mg, 0.99 mmol) and the reaction was stirred at room temperature. Once a clear solution was obtained, the reaction was placed in an ice bath and fitted with an addition funnel. A solution of 6-((R)-1-{7-[2-(5-methoxy-pyridin-2-yl)-acetyl]-2,7-diaza-spiro[3.5]non-2-yl}-indan-5-yl)-nicotinonitrile (11-1c, 379 mg, 0.85 mmol) in 1 mL of EtOH was added dropwise via the funnel over a period of 30 minutes. The solution became cloudy and was stirred overnight while warming to room temperature. After 18 hours, the reaction was concentrated. The crude product was purified on a Biotage (Biotage Inc.) 10 g reverse phase column, eluting with 0-50% acetonitrile in water to give the title compound 12 mg (8%). MS (ES+) 512.0 (M+H)+. 1H NMR (CD3OD) δ 1.61-1.75 (m, 4H), 1.90 (td, 1H), 2.24 (ddd, 1H), 2.83-2.94 (m, 1H), 3.05-3.17 (m, 1H), 3.20-3.27 (m, 2H), 3.48-3.56 (m, 5H), 3.83 (s, 4H), 3.85 (s, 2H), 4.04 (dd, 1H), 7.21-7.29 (m, 1H), 7.30-7.38 (m, 1H), 7.46 (d, 1H), 7.81-7.88 (m, 1H), 7.89-7.95 (m, 2H), 8.13 (d, 1H), 8.27 (dd, 1H), 9.05 (dd, 1H).

Workup

  1. customOnce a clear solution was obtained
  2. customthe reaction was placed in an ice bath
  3. customfitted with an addition funnel
  4. stirringwas stirred overnight
  5. temperaturewhile warming to room temperature
  6. concentrationthe reaction was concentrated
  7. customThe crude product was purified on a Biotage (Biotage Inc.) 10 g reverse phase column
  8. washeluting with 0-50% acetonitrile in water

Sources & evidence

ORD record
ord-7598c65603b940088eb5876de4da6785
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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