Ammonium Hydroxide → HCID 178491210、化合物

HRID 1014556ノート

反応式

HRID 1014556 の反応式
Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[C:13]([F:18])[CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:19]=[CH:20][N:21](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]=2[N:4]=1.[NH2:32][C:33]1[C:34]([O:47][CH3:48])=[CH:35][C:36]([CH3:46])=[C:37]([NH:39][C:40](=[O:45])[CH2:41][N:42]([CH3:44])[CH3:43])[CH:38]=1.[OH-].[NH4+:50]>FC(F)(F)CO.C1COCC1.CCOC(C)=O>[CH3:43][N:42]([CH3:44])[CH2:41][C:40]([NH:39][C:37]1[C:36]([CH3:46])=[CH:35][C:34]([O:47][CH3:48])=[C:33]([NH:32][C:3]2[NH:4][C:5]3=[N:21][CH:20]=[CH:19][C:6]3=[C:7]([NH:8][C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([F:18])[C:14]=3[C:15]([NH2:50])=[O:17])[N:16]=2)[CH:38]=1)=[O:45]

参加物

7

反応物 3

HCID 14923Ammonium HydroxideHCID 59441883N1-[5-amino-2-methyl-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamideHCID 673162535-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt

生成物 1

HCID 178491210HCID 178491210、化合物

試薬・触媒・溶媒 3

HCID 64092,2,2-Trifluoroethanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

To a suspension of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt (375 mg, 0.782 mmol) in 2,2,2-trifluoroethanol (10 mL) was added N1-[5-amino-2-methyl-4-(methyloxy)phenyl]-N2,N2-dimethylglycinamide (204 mg, 0.861 mmol). The resulting mixture was let stir at 60° C. for 45 min. Solvents were removed under reduced pressure to afford a green residue. Half of this material was dissolved in THF (10 mL) and aqueous ammonium hydroxide (27%) (30 mL, excess) was added. After stirring at rt for ˜36 h, the reaction was diluted with EtOAc and the organic layer was washed with water and a saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure. The residue was dissolved in dioxane (6 mL) in a microwave safe vessel and 2N NaOH (4 mL) was added. The reaction was then heated in a microwave at 120° C. for 15 min and then diluted with EtOAc. The organic layer was washed with water and a saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure and the residue purified by chromatography on SiO2 to afford 2-[(2-{[5-[(N,N-dimethylglycyl)amino]-4-methyl-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide (52 mg, 0.103 mmol) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.17 (s, 3 H) 2.32 (s, 6 H) 3.03 (s, 2 H) 3.84 (s, 3H) 6.25 (dd, J=3.30, 1.65 Hz, 1 H) 6.86-6.97 (m, 2 H) 6.97-7.03 (m, 1 H) 7.40-7.49 (m, 1 H) 7.52 (s, 1 H) 8.04 (br. s., 1 H) 8.11 (s, 1 H) 8.16 (s, 1 H) 8.47 (d, J=8.42 Hz, 1 H) 9.19 (s, 1 H) 10.53 (s, 1 H) 11.37 (br. s., 1 H). ESIMS (M+H)+=507.

後処理

  1. customSolvents were removed under reduced pressure
  2. customto afford a green residue
  3. stirringAfter stirring at rt for ˜36 h
  4. washthe organic layer was washed with water
  5. dry with materiala saturated brine solution and dried over sodium sulfate
  6. customSolvents were removed under reduced pressure
  7. dissolutionThe residue was dissolved in dioxane (6 mL) in a microwave safe vessel
  8. addition2N NaOH (4 mL) was added
  9. temperatureThe reaction was then heated in a microwave at 120° C. for 15 min
  10. additiondiluted with EtOAc
  11. washThe organic layer was washed with water
  12. dry with materiala saturated brine solution and dried over sodium sulfate
  13. customSolvents were removed under reduced pressure
  14. customthe residue purified by chromatography on SiO2

出典と根拠

ORDレコード
ord-0043276a1d344441a8b65341265b3e95
出典データセット
uspto-grants-2011_07
特許番号
US07981903B2

反応ノート

読み込み中…