Hydrochloric Acid → HCID 68737245, compound

HRID 529118Notes

Reaction equation

HRID 529118 reaction equation
C([O-])=O.[NH4+].C([N:12]1[CH2:17][CH2:16][C:15]2([C:25]3[C:20](=[CH:21][CH:22]=[CH:23][C:24]=3[CH2:26][NH:27][CH:28]([CH3:30])[CH3:29])[N:19]([C:31]3[C:32]4[C@H:39]([CH3:40])[CH2:38][CH2:37][C:33]=4[N:34]=[CH:35][N:36]=3)[CH2:18]2)[CH2:14][CH2:13]1)C1C=CC=CC=1.[ClH:41]>CO.C(Cl)Cl.CCOCC.[Pd]>[ClH:41].[ClH:41].[ClH:41].[CH3:40][C@H:39]1[C:32]2[C:31]([N:19]3[C:20]4[C:25](=[C:24]([CH2:26][NH:27][CH:28]([CH3:30])[CH3:29])[CH:23]=[CH:22][CH:21]=4)[C:15]4([CH2:16][CH2:17][NH:12][CH2:13][CH2:14]4)[CH2:18]3)=[N:36][CH:35]=[N:34][C:33]=2[CH2:37][CH2:38]1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 2723923Ammonium formateHCID 68764934HCID 68764934, compound

Product 1

HCID 68737245HCID 68737245, compoundYield 89%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

Ammonium formate (43 mg, 0.68 mmol) and 10% Pd/C (6 mg, 20% weight) was added to a solution of (R)—N-((1′-benzyl-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine (33 mg, 0.069 mmol) in MeOH (0.8 mL). The mixture was allowed to stir at reflux for 4 hours. After cooling, the reaction mixture was filtered through Celite. The filtrate was evaporated in vacuo. The residue was taken up in DCM, washed with saturated aqueous NaHCO3 solution and brine, dried and concentrated. The crude residue was purified by column chromatography (5% 7 N ammonia in MeOH/DCM) to yield the free base, which was taken up in DCM and acidified with 2N HCl in Et2O. Evaporation of the solvents in vacuo gave (R)—N-((1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine trihydrochloride (24 mg, 89%) as a solid. LCMS (APCI+) m/z 392 [M+H]+; Rt=1.77 min.

Workup

  1. temperatureat reflux for 4 hours
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture was filtered through Celite
  4. customThe filtrate was evaporated in vacuo
  5. washwashed with saturated aqueous NaHCO3 solution and brine
  6. customdried
  7. concentrationconcentrated
  8. customThe crude residue was purified by column chromatography (5% 7 N ammonia in MeOH/DCM)
  9. customto yield the free base, which
  10. customEvaporation of the solvents in vacuo

Sources & evidence

ORD record
ord-b28c9783f6194c90b017af65512c5494
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

Loading…