Hydrochloric Acid → PharmaGSID_48519

HRID 9727노트

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HRID 9727 반응식
[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]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 21988145(6-Amino-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol2회HCID 219881533-(2-bromophenyl)-7-methanesulfonyl-3,4-dihydro-1-methylpyrimido[4,5-d]pyrimidin-2(1H)-one

생성물 1

HCID 10345790PharmaGSID_48519

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

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온도
140 °C

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-c8ca5c2aedfc4492935406ddebc1bfe5
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07091345B2

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