Hydrochloric Acid → HCID 67316485、化合物

HRID 1014450

反応式

HRID 1014450 の反応式
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]

参加物

6

反応物 4

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

生成物 1

HCID 67316485HCID 67316485、化合物収率 168.5%

試薬・触媒・溶媒 1

HCID 64092,2,2-Trifluoroethanol溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-0dc5cd44c7194a0cb496a085bfee201c
出典データセット
uspto-grants-2011_07
特許番号
US07981903B2

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