Ammonium formate → HCID 71268444, compound

HRID 529124Notes

Reaction equation

HRID 529124 reaction equation
C([O-])=O.[NH4+].[C:5]([O:9][C:10](=[O:44])[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]2[N:19]([C:34]3[C:35]4[C@H:42]([CH3:43])[CH2:41][CH2:40][C:36]=4[N:37]=[CH:38][N:39]=3)[CH2:20][C:21]3([CH2:26][CH2:25][N:24](CC4C=CC=CC=4)[CH2:23][CH2:22]3)[C:14]=12)([CH3:8])([CH3:7])[CH3:6]>CO.[Pd]>[C:5]([O:9][C:10](=[O:44])[NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]2[N:19]([C:34]3[C:35]4[C@H:42]([CH3:43])[CH2:41][CH2:40][C:36]=4[N:37]=[CH:38][N:39]=3)[CH2:20][C:21]3([CH2:22][CH2:23][NH:24][CH2:25][CH2:26]3)[C:14]=12)([CH3:8])([CH3:6])[CH3:7]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 86651808HCID 86651808, compound

Product 1

HCID 71268444HCID 71268444, compoundYield 96.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

10% Pd/C (110 mg, 0.92 mmol) and ammonium formate (585 mg, 9.25 mmol) were added to (R)-tert-butyl(1′benzyl-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methylcarbamate (1.00 g, 1.85 mmol) in MeOH (20 mL). The reaction was heated to reflux for 6 hours, at which point the reaction was cooled to room temperature and filtered through Celite. The filtrate was concentrated to give (R)-tert-butyl(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methylcarbamate (800 mg, 96%), which was used without further purification. Boc2O (462 mg, 2.12 mmol) was added to a solution of (R)-tert-butyl(1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methylcarbamate (800 mg, 1.77 mmol) in DCM (25 mL). The reaction mixture was stirred overnight. The organic layer was washed with saturated aqueous NaHCO3 solution and brine, dried with MgSO4 and concentrated. The crude residue was purified by column chromatography (4:1 hexane:EtOAc) to give (R)-tert-butyl 4-((tert-butoxycarbonylamine)methyl)-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-carboxylate (856 mg, 88%) as a foam. LCMS (APCI+) m/z 550 [M+H]+; Rt=4.36 min.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 6 hours, at which
  3. filtrationfiltered through Celite
  4. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-aa0c20c340ae417c82caded68e1132bd
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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