N-3-Bromopropylphthalimide → (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

HRID 529095ノート

反応式

HRID 529095 の反応式
Cl.Cl.[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:11][N:10]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][CH2:24][C:20]=4[N:21]=[CH:22][N:23]=3)[C:7]2=[CH:8][CH:9]=1.Br[CH2:29][CH2:30][CH2:31][N:32]1[C:40](=[O:41])[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]1=[O:42].CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3([CH2:17][CH2:16][N:15]([CH2:29][CH2:30][CH2:31][N:32]4[C:40](=[O:41])[C:39]5[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=5)[C:33]4=[O:42])[CH2:14][CH2:13]3)[CH2:11][N:10]([C:18]3[C:19]4[C@H:26]([CH3:27])[CH2:25][CH2:24][C:20]=4[N:21]=[CH:22][N:23]=3)[C:7]2=[CH:8][CH:9]=1

参加物

5

反応物 3

HCID 21611N-3-BromopropylphthalimideHCID 81531DiisopropylethylamineHCID 68736280(R)-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4'-piperidine]dihydrochloride

生成物 1

HCID 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収率 63.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

A mixture of (R)-5-chloro-1-(5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)spiro[indoline-3,4′-piperidine]dihydrochloride (15 mg, 0.035 mmol), 2-(3-bromopropyl)isoindoline-1,3-dione (13 mg, 0.049 mmol), DIEA (0.018 mL, 0.11 mmol) and DMF (0.5 mL) was heated at about 150° C. in microwave for about 30 min. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by column chromatography (DCM:MeOH, 20:1) to give (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 (12 mg, 63%). LCMS (APCI+) m/z 542, 544 [M+H]+; Rt=3.79 min.

後処理

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between EtOAc and water
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washThe combined organic layers were washed with water and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (DCM:MeOH, 20:1)

出典と根拠

ORDレコード
ord-844173710afa41ceaca180d0616b221e
出典データセット
uspto-grants-2016_05
特許番号
US09346805B2

反応ノート

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