Potassium Carbonate → HCID 178502330、化合物

HRID 1751439ノート

反応式

HRID 1751439 の反応式
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]

参加物

6

反応物 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、化合物

生成物 1

HCID 178502330HCID 178502330、化合物収率 48%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-3098f0f4d53e4869bac850885ab60976
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

反応ノート

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