Potassium Carbonate → HCID 178455977、化合物

HRID 1509749ノート

反応式

HRID 1509749 の反応式
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:6]([C:16]2[NH:20][C:19]3[C:21]4[C:26]([CH:27]=[CH:28][C:18]=3[N:17]=2)=[CH:25][C:24]2[C:29]3[C:34]([CH2:35][O:36][C:23]=2[CH:22]=4)=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=3)[CH2:5]1.Br[C:47]1[NH:51][C:50]([C@@H:52]2[CH2:56][C@H:55]([CH3:57])[CH2:54][N:53]2[C:58](=[O:69])[C@@H:59]([NH:64][C:65](=[O:68])[O:66][CH3:67])[C@@H:60]([CH3:63])[CH2:61][CH3:62])=[N:49][CH:48]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=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.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:67][O:66][C:65]([NH:64][C@H:59]([C:58]([N:53]1[CH2:54][C@@H:55]([CH3:57])[CH2:56][C@H:52]1[C:50]1[NH:51][C:47]([C:32]2[CH:33]=[C:34]3[CH2:35][O:36][C:23]4[CH:22]=[C:21]5[C:26]([CH:27]=[CH:28][C:18]6[N:17]=[C:16]([C@@H:6]7[CH2:5][C@H:4]([CH2:3][O:2][CH3:1])[CH2:8][N:7]7[C:9]([O:11][C:12]([CH3:14])([CH3:15])[CH3:13])=[O:10])[NH:20][C:19]=65)=[CH:25][C:24]=4[C:29]3=[CH:30][CH:31]=2)=[CH:48][N:49]=1)=[O:69])[C@@H:60]([CH2:61][CH3:62])[CH3:63])=[O:68]

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 86688376HCID 86688376、化合物HCID 178495650HCID 178495650、化合物

生成物 1

HCID 178455977HCID 178455977、化合物収率 62.1%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 178418397HCID 178418397、化合物触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
95 °C

実験手順

(2S,4S)-Tert-butyl 4-(methoxymethyl)-2-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (856 mg, 1.4 mmol), methyl (2S,3S)-1-((2S,4S)-2-(5-bromo-1H-imidazol-2-yl)-4-methylpyrrolidin-1-yl)-3-methyl-1-oxopentan-2-ylcarbamate (932 mg, 2.1 mmol), Pd(PPh3)4 (162 mg, 0.14 mmol), PdCl2(dppf)2 (102 mg, 0.14 mmol), and K2CO3 (2M in H2O, 2.31 mL, 4.62 mmol) were combined in DMSO (8 mL) and dioxanes (8 mL). The mixture was degassed with bubbling Argon for 10 min then heated to 95° C. for 1 h. After cooling, the reaction mixture was diluted with EtOAc, and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (1% to 20% MeOH/EtOAc) to afford tert-butyl (2S,4S)-2-[9-(2-{(2S,4S)-1-[N-(methoxycarbonyl)-L-alloisoleucyl]-4-methylpyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (701 mg, 62%).

後処理

  1. customThe mixture was degassed with bubbling Argon for 10 min
  2. temperatureAfter cooling
  3. additionthe reaction mixture was diluted with EtOAc
  4. washwashed successively with saturated aqueous NaHCO3 and brine
  5. dry with materialThe organics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica column chromatography (1% to 20% MeOH/EtOAc)

出典と根拠

ORDレコード
ord-99d490f1de7e491682e6155070c165f7
出典データセット
uspto-grants-2015_12
特許番号
US09221833B2

反応ノート

読み込み中…