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

HRID 591597노트

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HRID 591597 반응식
[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

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
135 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-6222928783b64f1bbad32ddeca70e0a6
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238640B2

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