天然气 → 3-Tert-butyl-1-[6-(2,6-dichlorophenyl)-2-{[3-(diethylamino)propyl]amino}pyrido[2,3-d]pyrimidin-7-yl]urea

HRID 3417

反应方程式

HRID 3417 反应方程式
[NH2:1][C:2]1[C:3]([C:21]2[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:28])=[CH:4][C:5]2[CH:10]=[N:9][C:8]([NH:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])=[N:7][C:6]=2[N:20]=1.[H-].[Na+].[C:31]([N:35]=[C:36]=[O:37])([CH3:34])([CH3:33])[CH3:32].C>CN(C=O)C.O>[C:31]([NH:35][C:36]([NH:1][C:2]1[C:3]([C:21]2[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:28])=[CH:4][C:5]2[CH:10]=[N:9][C:8]([NH:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:18][CH3:19])[CH2:16][CH3:17])=[N:7][C:6]=2[N:20]=1)=[O:37])([CH3:34])([CH3:33])[CH3:32]

参与物

7

反应物 4

HCID 297天然气HCID 24758氢化钠HCID 62412叔丁基异氰酸酯HCID 53281146-(2,6-dichlorophenyl)-2-N-[3-(diethylamino)propyl]pyrido[2,3-d]pyrimidine-2,7-diamine

产物 1

HCID 53281153-Tert-butyl-1-[6-(2,6-dichlorophenyl)-2-{[3-(diethylamino)propyl]amino}pyrido[2,3-d]pyrimidin-7-yl]urea收率 27.9%

试剂、催化剂与溶剂 2

HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6228N,N-二甲基甲酰胺溶剂

实验过程

To a solution of 7-amino-6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidine (0.48 g) from Example 20 in DMF (5 mL) was added 60% sodium hydride suspension (46 mg), and the mixture was stirred for 1 hour at room temperature. To the reaction mixture was added t-butyl isocyanate (0.113 g), and the mixture was stirred for 18 hours. The reaction mixture was diluted with water and the insoluble material was collected by filtration. The solid was suspended in water (20 mL) and acidified with 1.0N HCl to form a solution. Activated charcoal was added to the solution, and the suspension filtered through celite, washing with water. The filtrate was made basic with 1.0N NaOH, and the insoluble product was collected by filtration and washed with water. A 180-mg sample of the product was further purified by reverse phase preparative HPLC on a C18 reverse phase column, eluting with a solvent gradient starting from 86% of 0.1% trifluoroacetic acid in water/14% acetonitrile to 14% of 0.1% trifluoroacetic acid in water/86% acetonitrile over a 22-minute time period to afford 165 mg of 1-tert-butyl-3-[6-(2,6-dichlorophenyl)-2-(3-diethylamino-propylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea, mp dec >80° C.

后处理

  1. stirringthe mixture was stirred for 18 hours
  2. filtrationthe insoluble material was collected by filtration
  3. customto form a solution
  4. filtrationthe suspension filtered through celite
  5. washwashing with water
  6. filtrationthe insoluble product was collected by filtration
  7. washwashed with water
  8. customA 180-mg sample of the product was further purified by reverse phase preparative HPLC on a C18 reverse phase column
  9. washeluting with a solvent gradient
  10. waitstarting from 86% of 0.1% trifluoroacetic acid in water/14% acetonitrile to 14% of 0.1% trifluoroacetic acid in water/86% acetonitrile over a 22-minute

来源与证据

ORD记录
ord-133c343446384739816db3dc834ba58e
来源数据集
uspto-grants-1998_03
专利号
US05733913

关联笔记

加载中…