1,2-Dimethoxyethane → (R)-6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80808ノート

反応式

HRID 80808 の反応式
COCCOC.[CH2:7]([N:14]1[CH2:43][CH2:42][C:17]2[N:18]=[C:19](Cl)[N:20]=[C:21]([N:22]3[CH2:27][CH2:26][N:25]([S:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[N+:37]([O-:39])=[O:38])(=[O:30])=[O:29])[C@H:24]([CH3:40])[CH2:23]3)[C:16]=2[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:44][C:45]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][C:52]=2B2OC(C)(C)C(C)(C)O2)[N:47]([S:63]([C:66]2[CH:72]=[CH:71][C:69]([CH3:70])=[CH:68][CH:67]=2)(=[O:65])=[O:64])[CH:46]=1.C([O-])([O-])=O.[Na+].[Na+]>CCOCC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:7]([N:14]1[CH2:43][CH2:42][C:17]2[N:18]=[C:19]([C:52]3[CH:51]=[CH:50][CH:49]=[C:48]4[C:53]=3[C:45]([CH3:44])=[CH:46][N:47]4[S:63]([C:66]3[CH:72]=[CH:71][C:69]([CH3:70])=[CH:68][CH:67]=3)(=[O:65])=[O:64])[N:20]=[C:21]([N:22]3[CH2:27][CH2:26][N:25]([S:28]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=4[N+:37]([O-:39])=[O:38])(=[O:30])=[O:29])[C@H:24]([CH3:40])[CH2:23]3)[C:16]=2[CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

参加物

8

反応物 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 712404273-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indoleHCID 86690263(R)-6-benzyl-2-chloro-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

生成物 1

HCID 71240482(R)-6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
140 °C

実験手順

1,2-Dimethoxyethane (6.75 mL) was added to a 20 mL microwave vial containing a mixture of (R)-6-benzyl-2-chloro-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (1.1 g, 2.03 mmol) and 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole (0.92 g, 2.23 mmol). Then 2M aqueous Na2CO3 was added and the reaction mixture was degassed via three argon/vacuum cycles, then charged with Pd(Ph3P)4 (0.234 g, 0.203 mmol). The vial was sealed and heated via microwave irradiation at 140° C. for 90 minutes. The mixture was then cooled to room temperature and diluted with Et2O and water. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic layers were combined dried over MgSO4, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography [55-75% ethyl acetate (containing 2% EtOH)/heptanes] to afford (R)-6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-4-(3-methyl-4-((2-nitrophenyl)sulfonyl)piperazin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. MS (ESI+) m/z 792.5 (M+H)+.

後処理

  1. additioncontaining
  2. customthe reaction mixture was degassed via three argon/vacuum cycles
  3. customThe vial was sealed
  4. temperatureThe mixture was then cooled to room temperature
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted two additional times with dichloromethane
  7. dry with materialThe organic layers were combined dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel flash chromatography [55-75% ethyl acetate (containing 2% EtOH)/heptanes]

出典と根拠

ORDレコード
ord-c9a0af297da54cc8890daf0de8cb7dd4
出典データセット
uspto-grants-2014_09
特許番号
US08846656B2

反応ノート

読み込み中…