Ammonium formate → (R)-tert-butyl 2-(1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylate

HRID 529139Notes

Reaction equation

HRID 529139 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[C@H:26]3[CH2:30][CH2:29][CH2:28][N:27]3[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:19]([C:38]3[C:39]4[C@H:46]([CH3:47])[CH2:45][CH2:44][C:40]=4[N:41]=[CH:42][N:43]=3)[CH2:18]2)[CH2:14][CH2:13]1)C1C=CC=CC=1>[Pd].CO>[CH3:47][C@H:46]1[C:39]2[C:38]([N:19]3[C:20]4[C:25](=[C:24]([C@H:26]5[CH2:30][CH2:29][CH2:28][N:27]5[C:31]([O:33][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:32])[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:43][CH:42]=[N:41][C:40]=2[CH2:44][CH2:45]1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 69813454(R)-tert-butyl 2-(1'-benzyl-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylate

Product 1

HCID 69811226(R)-tert-butyl 2-(1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylateYield 63%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of palladium on carbon (10% degussa typed, 10 mg), ammonium formate (50 mg, 0.80 mmol) and (R)-tert-butyl 2-(1′-benzyl-1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)pyrrolidine-1-carboxylate (15 mg, 0.026 mmol) in MeOH (5 mL) was heated to reflux for 5 hours. The reaction was filtered with a pad of celite and eluted with EtOAc (100 mL), and the filtrate was washed with water (10 mL). The organic layer was dried with Na2SO4, filtered and concentrated. The residue was purified with flash chromatography (eluted with 10% MeOH/ethyl acetate, 10% 7N NH3 in MeOH/ethyl acetate) to afford the product (R)-tert-butyl 2-(1-((R)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)pyrrolidine-1-carboxylate (8 mg, 63%) as a solid. 1H NMR (CDCl3, 400 MHz) δ 8.80 (s, 1H), 7.13 (t, 1H), 6.86-6.92 (m, 1H), 7.40 (d, 1H), 5.30-5.40 (m, 1H), 4.20-4.30 (m, 1H), 3.58-4.00 (m, 1H), 3.70-3.80 (m, 1H), 3.55-3.65 (m, 1H), 3.40-3.50 (m, 1H), 3.00-3.20 (m, 2H), 2.80-3.00 (m, 2H), 2.65-2.80 (m, 1H), 2.40-2.50 (m, 2H), 2.30-2.40 (m, 1H), 2.10-2.20 (m, 1H), 2.00-2.10 (m, 1H), 1.80-1.95 (m, 2H), 1.55-1.75 (m, 3H), 1.40-1.50 (m, 1H), 1.20 (s, 9H), 0.80-0.90 (m, 3H). MS (APCI+) [M+H]+ 490.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 hours
  3. filtrationThe reaction was filtered with a pad of celite
  4. washeluted with EtOAc (100 mL)
  5. washthe filtrate was washed with water (10 mL)
  6. dry with materialThe organic layer was dried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified with flash chromatography (eluted with 10% MeOH/ethyl acetate, 10% 7N NH3 in MeOH/ethyl acetate)

Sources & evidence

ORD record
ord-9a4768d14d6c47e08d53a7a0d5f889ed
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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