Potassium Carbonate → HCID 178502339、化合物

HRID 1751673ノート

反応式

HRID 1751673 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:31](=[CH:32][CH:33]=2)[C:15]2[NH:16][C:17]([C@@H:19]4[CH2:23][CH2:22][CH2:21][N:20]4[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:18][C:14]=2[CH:13]=[CH:12]3)O1.Br[C:36]1[C:37]([F:65])=[C:38]2[C:62](=[CH:63][CH:64]=1)[C:42]1[NH:43][C:44]([C@@H:46]3[CH2:50][CH2:49][CH2:48][N:47]3[C:51](=[O:61])[C@@H:52]([NH:56][C:57](=[O:60])[O:58][CH3:59])[CH:53]([CH3:55])[CH3:54])=[N:45][C:41]=1[CH:40]=[CH:39]2.C([O-])([O-])=O.[K+].[K+]>COCCOC.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]>[F:65][C:37]1[C:36]([C:9]2[CH:10]=[C:11]3[C:31](=[CH:32][CH:33]=2)[C:15]2[NH:16][C:17]([C@@H:19]4[CH2:23][CH2:22][CH2:21][N:20]4[C:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])=[O:25])=[N:18][C:14]=2[CH:13]=[CH:12]3)=[CH:64][CH:63]=[C:62]2[C:38]=1[CH:39]=[CH:40][C:41]1[N:45]=[C:44]([C@@H:46]3[CH2:50][CH2:49][CH2:48][N:47]3[C:51](=[O:61])[C@@H:52]([NH:56][C:57]([O:58][CH3:59])=[O:60])[CH:53]([CH3:54])[CH3:55])[NH:43][C:42]=12

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 178451892HCID 178451892、化合物HCID 178502338HCID 178502338、化合物

生成物 1

HCID 178502339HCID 178502339、化合物収率 71.2%

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 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

(S)-tert-butyl 2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (250 mg, 0.48 mmol) and methyl (S)-1-((S)-2-(7-bromo-6-fluoro-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (200 mg, 0.4 mmol), Pd(PPh3)4 (46 mg, 0.04 mmol), Pd(dppf)2Cl2 (29 mg, 0.04 mmol), and K2CO3 (2M in H2O, 0.67 mL, 1.34 mmoL) were combined in DME (6 mL). The mixture was degassed with bubbling N2 for 10 min the heated to 85° C. for 16 h. After cooling, the reaction mixture was diluted with EtOAc, and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc) to afford (S)-tert-butyl 2-(6′-fluoro-2′-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H,1′H-7,7′-binaphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (213 mg, 71%).

後処理

  1. customThe mixture was degassed with bubbling N2 for 10 min the
  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 MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified by silica column chromatography (0% to 30% MeOH/EtOAc)

出典と根拠

ORDレコード
ord-98683e761a8e4a6cb4197c039ec3a6d8
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

読み込み中…