Hydrochloric Acid → 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one

HRID 1014480

반응식

HRID 1014480 반응식
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[C:29]([F:31])[CH:28]=[C:27]([F:32])[C:23]=2[C:24]([NH2:26])=[O:25])[C:5]2[CH:10]=[CH:9][N:8]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])[C:6]=2[N:7]=1.[CH3:33][N:34]([CH2:36][C:37]([N:39]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45](N)[CH:46]=2)[CH2:41][CH2:40]1)=[O:38])[CH3:35].Cl.[I-].[K+]>FC(F)(F)CO.O1CCOCC1.ClCCl.C(=O)(O)[O-].[Na+]>[CH3:33][N:34]([CH3:35])[CH2:36][C:37]([N:39]1[C:47]2[C:42](=[CH:43][C:44]([O:49][CH3:50])=[C:45]([NH:3][C:2]3[N:26]4[C:4](=[N:21][C:22]5[C:23]([C:24]4=[O:25])=[C:27]([F:32])[CH:28]=[C:29]([F:31])[CH:30]=5)[C:5]4[CH:10]=[CH:9][N:8]([S:11]([C:14]5[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=5)(=[O:13])=[O:12])[C:6]=4[N:7]=3)[CH:46]=2)[CH2:41][CH2:40]1)=[O:38]

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-oneHCID 86644196HCID 86644196, 화합물

생성물 1

HCID 673166665-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2',3':4,5]pyrimido[6,1-b]quinazolin-7(3H)-one수율 95.1%

시약·촉매·용매 4

HCID 6344Dichloromethane용매HCID 64092,2,2-Trifluoroethanol용매HCID 312751,4-Dioxane용매HCID 516892Sodium Bicarbonate용매

반응 조건

온도
90 °C

실험 절차

To a suspension of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-4,6-difluorobenzamide (1.96 g, 4.1 mmol) in 2,2,2-trifluoroethanol (40 mL) was added 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (1.33 g, 5.33 mmol), hydrochloric acid as a 4.0M solution in dioxane (4.1 mL), and catalytic potassium iodide (<10 mg). The resulting slurry was stirred at 90° C. in a pressure vial for 40 hours, at which time all solids had completely dissolved. The resulting solution was cooled to room temperature and diluted with dichloromethane and saturated sodium bicarbonate as to adjust the aqueous layer to pH>10. The organic layer was washed with water and saturated brine solution and dried over sodium sulfate. Solvents were removed under reduced pressure to afford a yellow solid that was purified via trituration from diethyl ether to afford 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8,10-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (2.63 g, 3.90 mmol) as a yellow solid. (ESIMS (M+H)+=675)

후처리

  1. dissolutionhad completely dissolved
  2. temperatureThe resulting solution was cooled to room temperature
  3. washThe organic layer was washed with water and saturated brine solution
  4. dry with materialdried over sodium sulfate
  5. customSolvents were removed under reduced pressure
  6. customto afford a yellow solid
  7. customthat was purified via trituration from diethyl ether

출처 및 근거

ORD 기록
ord-1b6fa16d9e634e25beb9d4c923639d72
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981903B2

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