盐酸 → PharmaGSID_48519

HRID 9727笔记

反应方程式

HRID 9727 反应方程式
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13](S(C)(=O)=O)=[N:14][CH:15]=2)[N:10]([CH3:22])[C:9]1=[O:23].[OH:24][CH2:25][CH:26]1[O:31][C:30]2[CH:32]=[CH:33][C:34]([NH2:36])=[CH:35][C:29]=2[O:28][CH2:27]1.C(O)(C(F)(F)F)=O.Cl>CN1C(=O)CCC1>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:17][C:16]2[C:11](=[N:12][C:13]([NH:36][C:34]3[CH:33]=[CH:32][C:30]4[O:31][CH:26]([CH2:25][OH:24])[CH2:27][O:28][C:29]=4[CH:35]=3)=[N:14][CH:15]=2)[N:10]([CH3:22])[C:9]1=[O:23]

参与物

6

反应物 4

HCID 313盐酸HCID 6422三氟乙酸HCID 21988145(6-Amino-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol2 次HCID 219881533-(2-bromophenyl)-7-methanesulfonyl-3,4-dihydro-1-methylpyrimido[4,5-d]pyrimidin-2(1H)-one

产物 1

HCID 10345790PharmaGSID_48519

试剂、催化剂与溶剂 1

HCID 13387甲基吡咯烷酮溶剂

反应条件

温度
140 °C

实验过程

1.2 g 3-(2-bromo-phenyl)-3,4-dihydro-7-methanesulphonyl-1-methyl-pyrimido[4,5-d]pyrimidin-2(1H)-one and 1.54 g 2 hydroxymethyl-6-amino-1,4-benzodioxane (starting material b)) were mixed in 20 ml NMP. 0.348 g TFA were added and the mixture was heated to 140° C. for 7 hrs. The mixture was poured into 10% aqueous HCl and extracted with ethyl acetate. The aqueous phase was adjusted to pH>9 and extracted with CH2Cl2. The organic phases were combined and evaporated. The residue was suspended in CH2Cl2 at room temperature and solid impurities were filtered off. The filtrate was washed again with water to remove remainders of NMP, then evaporated. The residue was triturated with water, filtered and dried to give 0.6 g of the title product (mp: 156–158° C.). NMR (CDCl3, δ in ppm): 2.03 (broad s, 1 H); 3.48 (s, 3H); 3.89 (dd, 1H); 3.95 (dd, 1H); 4.15 (dd, 1H); 4.28 (m, 1H); 4.33 (dd, 1H); 4.55 (d, 1H); 4.71 (d, 1H); 6.89 (m, 1H); 6.98 (m, 2H); 7.25 (m, 1H); 7.40 (m, 3H); 7.71 (d, 1H); 7.98 (s, 1H). MS (APCI+): 498 (M+1), 420 (M-Br)

后处理

  1. extractionextracted with ethyl acetate
  2. extractionextracted with CH2Cl2
  3. customevaporated
  4. customwas suspended in CH2Cl2 at room temperature
  5. filtrationsolid impurities were filtered off
  6. washThe filtrate was washed again with water
  7. customto remove remainders of NMP
  8. customevaporated
  9. customThe residue was triturated with water
  10. filtrationfiltered
  11. customdried

来源与证据

ORD记录
ord-c8ca5c2aedfc4492935406ddebc1bfe5
来源数据集
uspto-grants-2006_08
专利号
US07091345B2

反应笔记

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