Ammonium formate → HCID 44197475, compound

HRID 529147Notes

Reaction equation

HRID 529147 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]([CH2:40][CH3:41])[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>CO.[Pd]>[CH2:40]([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]([CH3:29])[CH3:30])[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)[CH3:41]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 69812691HCID 69812691, compound

Product 1

HCID 44197475HCID 44197475, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Ammonium formate (21.5 mg, 0.341 mmol) was added to a mixture of (R)—N-((1′-benzyl-1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine (16.9 mg, 0.0341 mmol) and 10% Pd/C (10 mg) in methanol (1 mL) and refluxed. LCMS suggested debenzylation was complete after 2 hours. The reaction was concentrated and partitioned between DCM and saturated NaHCO3 solution. The aqueous portion was extracted a second time, and the combined organics were dried over Na2SO4. The DCM solution was decanted and concentrated under vacuum to provide the free-base product, (R)—N-((1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine. 1H NMR (CDCl3, 400 MHz) δ 8.62 (s, 1H), 7.31 (d, 1H), 7.14 (t, 1H), 6.93 (d, 1H), 3.85-4.01 (m, 4H), 3.29 (m, 1H), 3.08 (dd, 2H), 2.90-2.97 (m, 4H), 2.58 (m, 1H), 2.01-2.26 (m, 4H), 1.85 (m, 1H), 1.68 (dd, 2H), 1.46 (m, 2H), 1.03-1.11 (m, 7H), 0.78 (t, 3H). The product was dissolved in THF (1 mL) and converted to the hydrochloride salt by treatment with a 1M HCl solution in Et2O (1 mL). The reaction was sonicated, and the solvent was removed under vacuum providing (R)—N-((1-(5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)propan-2-amine trihydrochloride (11 mg, 0.021 mmol, 62% yield) as a powder. MS (APCI+) [M+H]: 406.3.

Workup

  1. temperaturerefluxed
  2. concentrationThe reaction was concentrated
  3. custompartitioned between DCM and saturated NaHCO3 solution
  4. extractionThe aqueous portion was extracted a second time
  5. dry with materialthe combined organics were dried over Na2SO4
  6. customThe DCM solution was decanted
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-9915889e174e4b21a0c5581f33d1bdaf
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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