Sodium Chloride → HCID 178496351, 화합물

HRID 1014478노트

반응식

HRID 1014478 반응식
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.[CH3:32][O:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][C:42]=1[NH2:43])[N:39]([C:44](=[O:48])[CH2:45][O:46][CH3:47])[CH2:38][CH2:37]2.[NH4+:49].[OH-].[Na+].[Cl-].[OH-].[K+].[OH-].[Na+]>C1COCC1.CCOC(C)=O>[F:18][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([NH:8][C:7]2[N:16]=[C:3]([NH:43][C:42]3[CH:41]=[C:40]4[C:36]([CH2:37][CH2:38][N:39]4[C:44](=[O:48])[CH2:45][O:46][CH3:47])=[CH:35][C:34]=3[O:33][CH3:32])[NH:4][C:5]3=[N:21][CH:20]=[CH:19][C:6]=23)[C:14]=1[C:15]([NH2:49])=[O:17]

참가 물질

9

반응물 6

HCID 5234Sodium ChlorideHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 594417515-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-amineHCID 673162535-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one HCl salt

생성물 1

HCID 178496351HCID 178496351, 화합물

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매2회

실험 절차

A thick white slurry of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (400 mg, 0.835 mmol) and 5-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-amine (197 mg, 0.835 mmol) in THF (15 mL) was heated at 80° C. for 17 h, cooled, then diluted with THF (20 mL) and a 30% aqueous NH4OH solution (50 mL). The reaction mixture was maintained for 17 h, then diluted with EtOAc (50 mL) and a saturated NaCl solution (25 mL). The organic layer was washed with a saturated NaCl solution (3×50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2. The crude product was triturated using Et2O, dissolved in dioxane (15 mL) and a 1N KOH solution (3.64 mL, 3.64 mmol) and then heated at 80° C. for 3 h. The resulting mixture was allowed to cool somewhat, diluted with EtOAc (100 mL) and a 2N NaOH solution (50 mL). The organic layer was washed with a 2N NaOH solution (2×50 mL), concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2 to obtain 2-fluoro-6-{[2-({5-(methyloxy)-1-[(methyloxy)acetyl]-2,3-dihydro-1H-indol-6-yl}amino)-1 H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzamide as a yellow solid (63 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.11 (t, J=8.15 Hz, 2H), 3.76 (s, 3H), 4.01 (t, J=8.33 Hz, 2H), 4.14 (s, 2H), 6.16-6.27 (m, 1H), 6.76-6.89 (m, 1H), 6.90-6.99 (m, 2H), 7.22-7.38 (m, 1H), 7.58 (s, 1H), 8.00 (s, 1H), 8.08 (s, 1H), 8.49 (d, J=8.42 Hz, 1H), 8.63 (s, 1H), 10.52 (s, 1H), 11.29 (s, 1H) a Me-O signal with 3 protons is missing, may overlap with water peak in sample; ESIMS (M+H)+=506.16.

후처리

  1. temperaturecooled
  2. temperatureThe reaction mixture was maintained for 17 h
  3. washThe organic layer was washed with a saturated NaCl solution (3×50 mL)
  4. concentrationconcentrated onto Celite
  5. custompurified by silica gel chromatography
  6. customThe crude product was triturated
  7. dissolutiondissolved in dioxane (15 mL)
  8. temperatureto cool somewhat
  9. washThe organic layer was washed with a 2N NaOH solution (2×50 mL)
  10. concentrationconcentrated onto Celite
  11. custompurified by silica gel chromatography

출처 및 근거

ORD 기록
ord-dfbfaf9b1c0c4cc9b3aaceb99e8d5e50
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981903B2

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