Water → 2-[(R)-5-(5-Carbamoyl-pyrazin-2-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester

HRID 1913468Notes

Reaction equation

HRID 1913468 reaction equation
O.OO.N[C:5]([NH2:7])=[O:6].[OH-].[Na+].C([C:12]1[N:13]=[CH:14][C:15]([C:18]2[CH:19]=[C:20]3[C:24](=[CH:25][CH:26]=2)[C@H:23]([N:27]2[CH2:30][C:29]4([CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]4)[CH2:28]2)[CH2:22][CH2:21]3)=[N:16][CH:17]=1)#N>CCO>[C:39]([O:38][C:36]([N:33]1[CH2:34][CH2:35][C:29]2([CH2:28][N:27]([C@H:23]3[C:24]4[C:20](=[CH:19][C:18]([C:15]5[CH:14]=[N:13][C:12]([C:5](=[O:6])[NH2:7])=[CH:17][N:16]=5)=[CH:26][CH:25]=4)[CH2:21][CH2:22]3)[CH2:30]2)[CH2:31][CH2:32]1)=[O:37])([CH3:42])([CH3:40])[CH3:41]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 31294Carbamide PeroxideHCID 67411806tert-Butyl 2-((R)-5-(5-cyanopyrazin-2-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

Product 1

HCID 674113452-[(R)-5-(5-Carbamoyl-pyrazin-2-yl)-indan-1-yl]-2,7-diaza-spiro[3.5]nonane-7-carboxylic acid tert-butyl esterYield 53.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A round-bottomed flask was charged with water (100 mL) and urea hydrogen peroxide (495 mg, 5.11 mmol). Sodium hydroxide (119 mg, 2.98 mmol) was added 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 tert-butyl 2-((R)-5-(5-cyanopyrazin-2-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (10-1a, 379 mg, 0.85 mmol) in 25 mL EtOH was added dropwise over a period of 30 minutes via the funnel. The reaction was warmed to room temperature and stirred overnight. The resulting white suspension was collected by vacuum filtration. The solids were washed with 50 mL water and air-dried to give 210 mg (53%) of the title compound as an off-white powder. MS (ES+) 464.4 (M+H)+. 1H NMR (DMSO-d6) δ 1.38 (s, 9H), 1.54-1.61 (m, 4H), 1.89 (d, 1H), 2.08 (s, 1H), 2.76-2.80 (m, 2H), 2.99 (d, 3H), 3.11 (d, 2H), 3.19-3.22 (m, 3H), 3.90 (d, 1H), 7.45 (d, 1H), 7.83 (br s, 1H), 8.01 (d, 1H), 8.08 (s, 1H), 8.23 (s, 1H), 9.20 (d, 1H), 9.24 (d, 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. temperatureThe reaction was warmed to room temperature
  5. stirringstirred overnight
  6. filtrationThe resulting white suspension was collected by vacuum filtration
  7. washThe solids were washed with 50 mL water
  8. customair-dried

Sources & evidence

ORD record
ord-1c1c61cfaa2a41448dbda17193f7b2b1
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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