Hydrochloric Acid → N-((1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methyl)acetamide dihydrochloride

HRID 529109Notes

Reaction equation

HRID 529109 reaction equation
C([N:8]1[CH2:13][CH2:12][C:11]2([C:21]3[C:16](=[CH:17][CH:18]=[CH:19][C:20]=3[CH2:22][NH:23][C:24](=[O:26])[CH3:25])[N:15]([C:27]3[C:28]4[C@H:35]([CH3:36])[CH2:34][C@@H:33]([OH:37])[C:29]=4[N:30]=[CH:31][N:32]=3)[CH2:14]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+].[ClH:42]>CO.C(Cl)Cl.CCOCC.[Pd]>[ClH:42].[ClH:42].[OH:37][C@H:33]1[C:29]2[N:30]=[CH:31][N:32]=[C:27]([N:15]3[C:16]4[C:21](=[C:20]([CH2:22][NH:23][C:24](=[O:26])[CH3:25])[CH:19]=[CH:18][CH:17]=4)[C:11]4([CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[CH2:14]3)[C:28]=2[C@H:35]([CH3:36])[CH2:34]1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 2723923Ammonium formateHCID 68759942N-((1'-benzyl-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methyl)acetamide

Product 1

HCID 68736588N-((1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-4-yl)methyl)acetamide dihydrochlorideYield 77%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-((1′-benzyl-1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)acetamide (19 mg, 0.038 mmol) in MeOH (0.4 mL) was added ammonium formate (24 mg, 0.38 mmol) and 10% Pd/C (4 mg, 20% weight). The mixture was allowed to stir at reflux for 4 h. After cooling, the reaction mixture was filtered through Celite. The filtrate was evaporated in vacuo. The crude residue was purified by column chromatography (4% 7 N ammonia in MeOH/DCM) to yield the free base, which was taken up in DCM and acidified with 2N HCl in Et2O. Removal of the solvents afforded N-((1-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-4-yl)methyl)acetamide dihydrochloride as a solid (12 mg, 77%). LCMS (APCI+) m/z 408 [M+H]+; Rt=1.74 min.

Workup

  1. temperatureat reflux for 4 h
  2. temperatureAfter cooling
  3. filtrationthe reaction mixture was filtered through Celite
  4. customThe filtrate was evaporated in vacuo
  5. customThe crude residue was purified by column chromatography (4% 7 N ammonia in MeOH/DCM)
  6. customto yield the free base, which
  7. customRemoval of the solvents

Sources & evidence

ORD record
ord-f6ebd91d1ffb4bd28ef3067bd5ffb159
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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