2-Piperidin-2-ylethanol → 1-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol

HRID 23189

反応式

HRID 23189 の反応式
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH:12]=[CH:11][N:10]=[CH:9]2)[N:3]=1.[NH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]1[CH2:19][CH2:20][OH:21].CCN(C(C)C)C(C)C>CN(C=O)C>[N:8]1([C:4]2[N:3]=[C:2]([N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]3[CH2:19][CH2:20][OH:21])[CH:7]=[CH:6][N:5]=2)[CH:12]=[CH:11][N:10]=[CH:9]1

参加物

5

反応物 3

HCID 151442-Piperidin-2-ylethanolHCID 81531DiisopropylethylamineHCID 106074834-chloro-2-(1H-imidazol-1-yl)pyrimidine

生成物 1

HCID 224879671-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol収率 46.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

The above synthesis may be carried out as follows: To DMF (100 ml) was added 4-chloro-2-imidazol-1-ylpyrimidine (0.50 g, 2.77 mmol), 2-piperidineethanol (0.359 g, 2.77 mmol), and Hünig's base (0.536 g, 4.15 mmol). After heating at 80° C. for 5 hours, the solvent was removed in vacuo and the residue was chromatographed (CH2Cl2/MeOH, 19/1) to give 349 mg (46% ) of 1-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol (the compound of formula (XVI)), (1H NMR (CDCl3) δ 8.54 (s, 2), 8.11 (d, 1), 7.82 (t, 1), 7.11 (d, 1), 6.44 (d, 1), 3.60 (m, 2), 3.03 (m, 1), 1.77 (m); MS: 274 (M+H)+). To a solution of 1-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol (25 mg, 0.092 mmol) dissolved in DMF (5 ml) was added NaH (60% dispersion in oil, 5.5 mg, 0.14 mmol) followed by piperonyl chloride (17 mg, 0.10 mmol) and t-butyl ammonium chloride. After stirring for 16 hours at 80° C., the solvent was removed in vacuo and the residue was partitioned with saturated NH4Cl and CH2Cl2. The organic layer was separated, dried (MgSO4), the solvent removed in vacuo, and the residue chromatographed (CH2Cl2/MeOH, 19/1) to give 13 mg (35%) of 4-[2-[[(1,3-benzodioxol-5-yl)methoxy]ethyl]piperidin-1-yl]-2-(1H-imidazol-1-yl)pyrimidine (the compound of formula (Icc)); 1H NMR (CDCl3) δ 8.52 (s, 1), 8.05 (d, 1), 8.05 (d, 1), 7.80 (s, 1), 7.09 (s, 1), 6.73 (m, 3), 6.45 (d, 1), 5.93 (s, 2), 4.30 (s, 2), 3.45 (m, 2), 2.95 (m, 1), 1.55 (m); MS: 408.7 (M+H)+.

後処理

  1. customThe above synthesis
  2. customthe solvent was removed in vacuo
  3. customthe residue was chromatographed (CH2Cl2/MeOH, 19/1)

出典と根拠

ORDレコード
ord-7d9196d8f32e4225a61ee5e9574da137
出典データセット
uspto-grants-2005_02
特許番号
US06849739B2

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