Potassium Carbonate → HCID 178502339, 화합물

HRID 1751673노트

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HRID 1751673 반응식
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

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 178451892HCID 178451892, 화합물HCID 178502338HCID 178502338, 화합물

생성물 1

HCID 178502339HCID 178502339, 화합물수율 71.2%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

(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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-98683e761a8e4a6cb4197c039ec3a6d8
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

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