Methylamine → (R)-3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-yl)propan-1-amine

HRID 529096Notes

Reaction equation

HRID 529096 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][N:19]4C(=O)C5C(=CC=CC=5)C4=O)[CH2:12][CH2:11]3)[CH2:9][N:8]([C:30]3[C:31]4[C@H:38]([CH3:39])[CH2:37][CH2:36][C:32]=4[N:33]=[CH:34][N:35]=3)[C:5]2=[CH:6][CH:7]=1.CN>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][NH2:19])[CH2:14][CH2:15]3)[CH2:9][N:8]([C:30]3[C:31]4[C@H:38]([CH3:39])[CH2:37][CH2:36][C:32]=4[N:33]=[CH:34][N:35]=3)[C:5]2=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 68764576(R)-2-(3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-yl)propyl)isoindoline-1,3-dione

Product 1

HCID 44198402(R)-3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]-1'-yl)propan-1-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of (R)-2-(3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-yl)propyl)isoindoline-1,3-dione (9 mg, 0.02 mmol) and 2M MeNH2 in MeOH (0.5 mL) was stirred at about room temperature overnight. The solvent was evaporated. The residue was purified by column chromatography (DCM:7N ammonia in MeOH, 8:1) to give (R)-3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-yl)propan-1-amine as a free base, which was taken up in DCM and acidified with 2N HCl in ether. Removal of the solvents under reduced pressure afforded (R)-3-(5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]-1′-yl)propan-1-amine trihydrochloride (5 mg, 74%) as a solid. LCMS (APCI+) m/z 412, 414 [M+H]+; Rt=2.47 min.

Workup

  1. customThe solvent was evaporated
  2. customThe residue was purified by column chromatography (DCM:7N ammonia in MeOH, 8:1)

Sources & evidence

ORD record
ord-f1e74247df3647db8376246732466bb1
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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