Potassium Carbonate → HCID 178502330, 화합물

HRID 1751439노트

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HRID 1751439 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([CH:13]3[C@@H:18]4[CH2:19][C@@H:15]([CH2:16][CH2:17]4)[N:14]3[C:20](=[O:31])[C@@H:21]([NH:26][C:27](=[O:30])[O:28][CH3:29])[C@H:22]([O:24][CH3:25])[CH3:23])=[N:10][CH:9]=2)=[C:4]([F:32])[CH:3]=1.[CH3:33][CH:34]([CH3:70])[C@H:35]([NH:65][C:66](=[O:69])[O:67][CH3:68])[C:36](=[O:64])[N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C:42]1[NH:46][C:45]2[C:47]3[C:52]([CH:53]=[CH:54][C:44]=2[N:43]=1)=[CH:51][C:50](B1OC(C)(C)C(C)(C)O1)=[CH:49][CH:48]=3.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>[CH3:68][O:67][C:66]([NH:65][C@@H:35]([CH:34]([CH3:70])[CH3:33])[C:36]([N:37]1[CH2:41][CH2:40][CH2:39][C@H:38]1[C:42]1[NH:46][C:45]2[C:47]3[C:52]([CH:53]=[CH:54][C:44]=2[N:43]=1)=[CH:51][C:50]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([CH:13]4[C@@H:18]5[CH2:19][C@@H:15]([CH2:16][CH2:17]5)[N:14]4[C:20](=[O:31])[C@@H:21]([NH:26][C:27](=[O:30])[O:28][CH3:29])[C@H:22]([O:24][CH3:25])[CH3:23])=[N:10][CH:9]=2)=[C:4]([F:32])[CH:3]=1)=[CH:49][CH:48]=3)=[O:64])=[O:69]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 67681773Methyl (2S,3R)-1-((1R,4S)-3-(5-(4-bromo-2-fluorophenyl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methoxy-1-oxobutan-2-ylcarbamateHCID 178502307HCID 178502307, 화합물

생성물 1

HCID 178502330HCID 178502330, 화합물수율 48%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

실험 절차

Methyl (2S,3R)-1-((1R,4S)-3-(5-(4-bromo-2-fluorophenyl)-1H-imidazol-2-yl)-2-azabicyclo[2.2.1]heptan-2-yl)-3-methoxy-1-oxobutan-2-ylcarbamate (162 mg, 0.318 mmol), methyl (S)-3-methyl-1-oxo-1-((S)-2-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-naphtho[1,2-d]imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (199 mg, 0.382 mmol), Pd(PPh3)4 (37 mg, 0.0318 mmol) and K2CO3 (2M in H2O, 0.4 mL, 0.8 mmol) were suspended in DME (3 mL). The reaction mixture was degassed with N2 for 11 min then heated to reflux for 2.5 h. Upon completion, the reaction mixture was diluted with MeOH, filtered over a thiol SPE column and concentrated. The crude residue was purified by silica column chromatography (0% to 50% MeOH/EtOAc) to afford the title compound (125 mg, 48%). (ESI) m/z 823 [M+H]+.

후처리

  1. customThe reaction mixture was degassed with N2 for 11 min
  2. temperaturethen heated
  3. temperatureto reflux for 2.5 h
  4. additionUpon completion, the reaction mixture was diluted with MeOH
  5. filtrationfiltered over a thiol SPE column
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica column chromatography (0% to 50% MeOH/EtOAc)

출처 및 근거

ORD 기록
ord-3098f0f4d53e4869bac850885ab60976
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

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