Diisopropylethylamine → [2-(4-Chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amine

HRID 2110681ノート

反応式

HRID 2110681 の反応式
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=2)[N:5]=[C:4]([O:18][CH3:19])[N:3]=1.C(N(CC)C(C)C)(C)C.[CH3:29][CH:30]([NH2:39])[CH2:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1.Cl>C1COCC1>[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([CH2:31][CH:30]([NH:39][C:2]2[CH:7]=[C:6]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH3:17])[CH:9]=3)[N:5]=[C:4]([O:18][CH3:19])[N:3]=2)[CH3:29])=[CH:37][CH:36]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 107161p-Chloroamphetamine hydrochlorideHCID 576361174-Chloro-6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidine2 回

生成物 1

HCID 11524458[2-(4-Chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amine収率 25.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 4-chloro-6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidine [140 mg, 0.5 mmol, Intermediate (50)] and N,N-diisopropylethylamine (392 μL, 2.25 mmol) in THF (1.7 mL) is added DL-p-chloroamphetamine hydrochloride (154.6 mg, 0.75 mmol, Intermediate (51)]. The mixture is heated to reflux for 2 hours and quenched with water (20 mL) and extracted twice with EtOAc (20 mL). The combined extracts are concentrated and the residue is subjected to flash column chromatography on silica gel eluting with 0 to 50% EtOAc in heptane gradient to afford [2-(4-chloro-phenyl)-1-methyl-ethyl]-[6-(3,4-dimethoxy-phenyl)-2-methoxy-pyrimidin-4-yl]-amine [52.7 mg, 25.5%, Example 43(a)]. LCMS: RT=2.66 minutes, MS: 414 (M+H). 1H NMR (300 MHz, CDCl3): δ 7.65 (1H, d, J=0.066 Hz), 7.53 (1H, dd, J=0.066, 0.028), 7.28 (2H, d, J=0.028 Hz), 7.14 (2H, d, J=0.028 Hz), 6.93 (1H, d, J=0.028 Hz), 6.31 (1H, s), 4.72 (1H, s), 4.34 (1H, s), 4.04 (3H, s), 3.99 (3H, s), 3.95 (3H, s), 2.89 (2H, qd, J=0.045, 0.022 Hz), 1.79 (1H, s), 1.24 (3H, d, J=0.22 Hz). IC50=1726 nM

後処理

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 2 hours
  3. customquenched with water (20 mL)
  4. extractionextracted twice with EtOAc (20 mL)
  5. concentrationThe combined extracts are concentrated

出典と根拠

ORDレコード
ord-1a704cf096ac49329541fd1db475140e
出典データセット
uspto-grants-2009_04
特許番号
US07517889B2

反応ノート

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