Hydrochloric Acid → PharmaGSID_48519

HRID 9727ノート

反応式

HRID 9727 の反応式
[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]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 21988145(6-Amino-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol2 回HCID 219881533-(2-bromophenyl)-7-methanesulfonyl-3,4-dihydro-1-methylpyrimido[4,5-d]pyrimidin-2(1H)-one

生成物 1

HCID 10345790PharmaGSID_48519

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
140 °C

実験手順

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)

後処理

  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

出典と根拠

ORDレコード
ord-c8ca5c2aedfc4492935406ddebc1bfe5
出典データセット
uspto-grants-2006_08
特許番号
US07091345B2

反応ノート

読み込み中…