p-Toluenesulfonic acid monohydrate → 2-(4-(4-Hydroxypiperidin-1-yl)phenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one

HRID 591597ノート

反応式

HRID 591597 の反応式
[NH2:1][C:2]1[N:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:29]=[CH:28][C:25]([CH:26]=O)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S(=O)(O)[O-].[Na+]>CN(C)C(=O)C>[OH:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:29]=[CH:28][C:25]([C:26]3[NH:6][C:4](=[O:5])[C:3]4[C:7]([O:13][CH3:14])=[CH:8][C:9]([O:11][CH3:12])=[N:10][C:2]=4[N:1]=3)=[CH:24][CH:23]=2)[CH2:18][CH2:17]1

参加物

6

反応物 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 127174464-(4-Hydroxypiperidin-1-yl)benzaldehydeHCID 23665763Sodium BisulfiteHCID 666066902-Amino-4,6-dimethoxy-nicotinamide

生成物 1

HCID 1359390862-(4-(4-Hydroxypiperidin-1-yl)phenyl)-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
135 °C

実験手順

A mixture of 2-amino-4,6-dimethoxy-nicotinamide (0.60 g, 3.0 mmol), 4-(4-hydroxy-piperidin-1-yl)-benzaldehyde (0.81 g, 3.9 mmol), p-toluenesulfonic acid monohydrate (1.25 g, 6.6 mmol) and sodium bisulfite (1.06 g, 6.0 mmol) in N,N-dimethylacetamide (8.0 mL) was stirred at 135° C. under N2 for 16 hours and then cooled to room temperature. The mixture was concentrated to dryness under reduced pressure. Water (40 mL) was added to the residue and stirred for 0.5 hours. The precipitate was filtered and the solid was rinsed with water and air-dried. The crude solid was purified by column chromatography (silica gel 230-400 mesh; eluting with 4% methanol in dichloromethane) to afford the title compound, as a yellow solid. Yield: 0.29 g (25.2%). MP 284-286° C. 1H NMR (400 MHz, DMSO-d6): δ 12.09 (s, 1H), 8.12 (d, J=8.8 Hz, 2H), 7.02 (d, J=8.8 Hz, 2H), 6.32 (s, 1H), 4.73 (d, J=4.4 Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H), 3.72 (m, 3H), 3.05 (m, 2H), 1.80 (m, 2H), 1.43 (m, 2H). MS (ES+) m/z: 383.06 (M+1).

後処理

  1. temperaturecooled to room temperature
  2. concentrationThe mixture was concentrated to dryness under reduced pressure
  3. additionWater (40 mL) was added to the residue
  4. stirringstirred for 0.5 hours
  5. filtrationThe precipitate was filtered
  6. washthe solid was rinsed with water
  7. customair-dried
  8. customThe crude solid was purified by column chromatography (silica gel 230-400 mesh; eluting with 4% methanol in dichloromethane)

出典と根拠

ORDレコード
ord-6222928783b64f1bbad32ddeca70e0a6
出典データセット
uspto-grants-2016_01
特許番号
US09238640B2

反応ノート

読み込み中…