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Potassium Carbonate → HCID 178438799, 화합물

HRID 1751642
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HRID 1751642 반응식
[CH3:1][CH:2]([CH3:39])[C@H:3]([NH:34][C:35](=[O:38])[O:36][CH3:37])[C:4](=[O:33])[N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[C:17]([C:30]#[C:31][CH3:32])[CH:16]=2)=[CH:13][N:14]=1.Br[C:41]1[CH:42]=[C:43]2[C:66](=[CH:67][CH:68]=1)[C:47]1[NH:48][C:49]([C@@H:51]3[CH2:55][C@H:54]([CH2:56][O:57][CH3:58])[CH2:53][N:52]3[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])=[N:50][C:46]=1[CH:45]=[CH:44]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]>[CH3:37][O:36][C:35]([NH:34][C@@H:3]([CH:2]([CH3:39])[CH3:1])[C:4]([N:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]1[NH:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([C:42]3[CH:41]=[C:68]4[C:45](=[CH:44][CH:43]=3)[C:46]3[NH:50][C:49]([C@@H:51]5[CH2:55][C@H:54]([CH2:56][O:57][CH3:58])[CH2:53][N:52]5[C:59]([O:61][C:62]([CH3:63])([CH3:64])[CH3:65])=[O:60])=[N:48][C:47]=3[CH:66]=[CH:67]4)=[C:17]([C:30]#[C:31][CH3:32])[CH:16]=2)=[CH:13][N:14]=1)=[O:33])=[O:38]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 3

HCID 11430Potassium CarbonateHCID 86708797Methyl (S)-3-methyl-1-oxo-1-((S)-2-(5-(3-(prop-1-ynyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamateHCID 178495670HCID 178495670, 화합물

생성물 1

HCID 178438799HCID 178438799, 화합물수율 30%

시약·촉매·용매 3

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 178418397HCID 178418397, 화합물촉매
HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
85 °C

실험 절차

Methyl (S)-3-methyl-1-oxo-1-((S)-2-(5-(3-(prop-1-ynyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (153 mg, 0.28 mmol), (2S,4S)-tert-butyl 2-(7-bromo-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (158 mg, 0.34 mmol), Pd(PPh3)4 (32 mg, 0.028 mmol), Pd(dppf)2Cl2 (20 mg, 0.028 mmol), and K2CO3 (2M in H2O, 0.46 mL, 0.92 mmoL) were combined in DME (4 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 (2S,4S)-tert-butyl 2-(7-(4-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-2-(prop-1-ynyl)phenyl)-1H-naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (66 mg, 30%).

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-3406f81bf54d4390ab2b310f257e455e
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09156823B2

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