Acetonitrile → N1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-N2-methylethane-1,2-diamine

反応式

[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1.[CH:19]([N:22]([CH:25](C)C)CC)(C)[CH3:20].C(#[N:30])C>>[Cl:1][C:2]1[N:3]=[C:4]([NH:30][CH2:20][CH2:19][NH:22][CH3:25])[C:5]2[CH2:10][CH2:9][CH:8]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:6]=2[N:7]=1

参加物

反応物 3

HCID 6342Acetonitrile

HCID 81531Diisopropylethylamine

HCID 580754242,4-Dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[D]pyrimidine

生成物 1

HCID 86668110N1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-N2-methylethane-1,2-diamine収率 70.6%

実験手順

To a solution of 2,4-dichloro-7-(4-fluorophenyl)-6,7-dihydro-5H cyclopenta[d]pyrimidine (2.0 g, 7.06 mmol) in acetonitrile (50 mL) was added diisopropylethylamine (1.369 g, 10.60 mmol) followed by N-1-methylethane-1,2-diamine (0.628 g, 8.48 mmol) at room temperature. The reaction mixture was stirred at rt for 18 h. The solvent was removed under reduced pressure and the residue was taken in dichloromethane (10 mL) and silica (2 g). The resultant slurry of the compound on silica was subjected to flash chromatography using a Teledyne Isco instrument (12 g RediSep silica column, 10% methanol in chloroform) to get N1-(2-chloro-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)-N2-methylethane-1,2-diamine (1.6 g, 70.6%) as a light brown solid. LC-MS (M+H)+=321.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.13 (2H, br s), 7.22-7.11 (4H, m), 4.21-4.17 (1H, t, J=8.0 Hz), 3.82-3.79 (2H, m), 3.27 (3H, s), 3.19-3.04 (4H, m), 2.55-2.54 (1H, m), 1.99-1.98 (1H, m).

後処理

customThe solvent was removed under reduced pressure

出典と根拠

ORDレコード: ord-087692eff4cd4c39a4346fb4f6758ced
出典データセット: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US08637523B2

反応ノート

読み込み中…