Hydrochloric Acid → HCID 67316485, 화합물

HRID 1014450

반응식

HRID 1014450 반응식
Cl[C:2]1[N:3]=[C:4]([NH:21][C:22]2[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=2[C:24](N)=[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.[CH3:32][N:33]([CH2:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([O:48][CH3:49])=[C:44]([NH2:47])[CH:45]=2)[CH2:40][CH2:39]1)=[O:37])[CH3:34].Cl.ClCCl>FC(F)(F)CO>[CH3:32][N:33]([CH3:34])[CH2:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([O:48][CH3:49])=[C:44]([NH:47][C:2]3[N:3]4[C:4](=[N:21][C:22]5[C:23]([C:24]4=[O:25])=[C:27]([F:31])[CH:28]=[CH:29][CH:30]=5)[C:5]4[CH:10]=[CH:9][N:8]([S:11]([C:14]5[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=5)(=[O:12])=[O:13])[C:6]=4[N:7]=3)[CH:45]=2)[CH2:40][CH2:39]1)=[O:37]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-oneHCID 86644188HCID 86644188, 화합물

생성물 1

HCID 67316485HCID 67316485, 화합물수율 168.5%

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

반응 조건

온도
90 °C

실험 절차

Two separate suspensions of 2-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-6-fluorobenzamide (6.25 g, 13.59 mmol), 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (3.90 g, 15.63 mmol), KI (2.256 g, 13.59 mmol), and HCl (4.0M Solution in dioxane, 13.59 ml, 54.4 mmol) in 2,2,2-trifluoroethanol (200 ml) were warmed at 90° C. for 16 hours in sealed pressure flasks. The reactions were cooled, combined, and poured into dichloromethane/saturated sodium bicarbonate and the organic layers taken to a residue under reduced pressure and triturated with diethyl ether to afford 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (15 g, 22.9 mmol, 84%). A solution of the 5-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (500 mg, 0.763 mmol) and 2.0M ethylamine in tetrahydrofuran (2.67 ml, 5.34 mmol) in THF(10 ml) was stirred at room temperature for 16 hours. The crude reaction mixture was stripped onto celite and purified by chromatography on SiO2 to afford 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-N-ethyl-6-fluorobenzamide (275 mg, 0.392 mmol, 51.5%) as a pale brown solid. A suspension of 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-N-ethyl-6-fluorobenzamide (0.275 g, 0.392 mmol) in 1,4 dioxane/2.0 N NaOH was heated at 120° C. for 11 minutes in a microwave. The resulting solution was poured into ethyl acetate/saturated sodium chloride and the organic layer was dried over sodium sulfate, filtered, stripped onto celite, and purified by chromatography to afford 2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-N-ethyl-6-fluorobenzamide (150 mg, 0.274 mmol, 70%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.21 (s, 1H), 9.91 (s, 1H), 8.59 (s, 1H), 8.55 (t, J=5.77 Hz, 1H), 8.27 (d, J=8.42 Hz, 1H), 7.52 (s, 1H), 7.20-7.34 (m, 1H), 6.87-6.95 (m, 2H), 6.84 (d, J=9.34 Hz, 1H), 6.22 (s, 1H), 4.13 (t, J=8.42 Hz, 2H), 3.73 (s, 3H), 3.18-3.26 (m, 2H), 3.13 (s, 2H), 3.07 (t, J=8.24 Hz, 2H), 2.21 (s, 6H), 0.97-1.13 (m, 3H). ESIMS (M+H)+=547.

후처리

  1. temperatureThe reactions were cooled
  2. customtriturated with diethyl ether

출처 및 근거

ORD 기록
ord-0dc5cd44c7194a0cb496a085bfee201c
출처 데이터셋
uspto-grants-2011_07
특허 번호
US07981903B2

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