Dimethyl Sulfoxide → (2RS, 3R)-3-(6-Benzylamino-9-isopropyl-9H-purin-2-ylamino)-pentan-2-ol

HRID 1432395ノート

反応式

HRID 1432395 の反応式
[CH2:1]([NH:8][C:9]1[N:17]=[C:16](F)[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(C)=O.[NH2:26][C@H:27]([CH2:31][CH3:32])[CH:28]([OH:30])[CH3:29]>C(Cl)Cl.CCOCC.CO>[CH2:1]([NH:8][C:9]1[N:17]=[C:16]([NH:26][C@H:27]([CH2:31][CH3:32])[CH:28]([OH:30])[CH3:29])[N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[CH:19]([CH3:21])[CH3:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 679Dimethyl SulfoxideHCID 17954009Benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amineHCID 86760975(2RS,3R)-3-amino-pentan-2-ol

生成物 1

HCID 24782040(2RS, 3R)-3-(6-Benzylamino-9-isopropyl-9H-purin-2-ylamino)-pentan-2-ol

試薬・触媒・溶媒 1

HCID 22565053DCM ether MeOH溶媒

実験手順

To a stirred solution of benzyl-(2-fluoro-9-isopropyl-9H-purin-6-yl)-amine (0.34 g, 1.19 mmol) in BunOH/DMSO (5 mL, 4:1) at RT under Ar was added Pri2NEt (2.0 mL, 11.48 mmol) followed by (2RS,3R)-3-amino-pentan-2-ol (0.16 g, 1.55 mmol). The reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 48 h, when TLC (55:40:5 CH2Cl2 Et2O/MeOH) indicated the appearance of a lower running product together with some desired product. The reaction mixture was allowed to cool to RT and the solvent was evaporated in vacuo. The residue was partitioned between CH2Cl2 (100 mL) and H2O (200 mL), the aqueous phase was extracted with more CH2Cl2 (3×50 mL), and the combined organic phase was washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient column chromatography on silica gel eluted with CH2Cl2/Et2O/MeOH (60:40:0→60:40:4) to afford thee title compound as a white solid (0.03 g, 7%). Mp 43-46° C. 1H-NMR (d6-DMSO, 250 MHz): δ 0.75-0.85 (m, 3H, —NHCH(CH2CH3)CH(CH3)OH), 0.95-1.03 (m, 3H, —NHCH(CH2CH3)CH(CH3)OH) 1.19-1.77 (m, 8H, —NHCH(CH2CH3)CH(CH3)OH+CH(CH3)2), 3.60+3.73 (2×m, 1H, —NHCH(CH2CH3)CH(CH3)OH), 4.44-4.78 (m, 4H, —HNCH2-Bz+—NHCH(CH2CH3)CH(CH3)OH+—CH(CH3)2), 5.57+5.87 (2×d, 1H, J=9.958+7.74 Hz, —NHCH(CH2CH3)CH(CH3)OH), 7.18-7.36 (m, 5H, Bz), 7.77 (bs, 2H, —N═CH—N—+—HNCH2-Bz). FAB-MS m/z (relative intensity): 369 ([M+H]+, 100), 323 (96), 233 (30). Accurate Mass (M+H): Actual: 369.2403, Measured: 369:2393 Microanalysis (Expected:Measured) C20H28N6O.0.5H2O: C, 63.64:64.17; H, 7.74:7.56; N, 22.26:21.38.

後処理

  1. customThe reaction mixture was placed in a preheated oil bath at 140° C.

出典と根拠

ORDレコード
ord-53861204c5c6428f820206f960711c07
出典データセット
uspto-grants-2009_11
特許番号
US07612079B2

反応ノート

読み込み中…