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 529096ノート

反応式

HRID 529096 の反応式
[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

参加物

4

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-f1e74247df3647db8376246732466bb1
出典データセット
uspto-grants-2016_05
特許番号
US09346805B2

反応ノート

読み込み中…