Potassium Carbonate → HCID 178495652, 화합물

HRID 1431807노트

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HRID 1431807 반응식
[CH3:1][O:2][CH2:3][C@@H:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:6]([C:16]2[NH:20][C:19]3[C:21]4[C:26]([CH:27]=[CH:28][C:18]=3[N:17]=2)=[CH:25][C:24]2[C:29]3[C:34]([CH2:35][O:36][C:23]=2[CH:22]=4)=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=3)[CH2:5]1.Br[C:47]1[CH:48]=[CH:49][C:50]2[N:54]=[C:53]([C@@H:55]3[CH2:59][CH2:58][CH2:57][N:56]3[C:60](=[O:70])[C@@H:61]([NH:65][C:66](=[O:69])[O:67][CH3:68])[CH:62]([CH3:64])[CH3:63])[NH:52][C:51]=2[CH:71]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.CN(C)C=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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]>[C:12]([O:11][C:9]([N:7]1[CH2:8][C@@H:4]([CH2:3][O:2][CH3:1])[CH2:5][C@H:6]1[C:16]1[NH:20][C:19]2[C:21]3[C:26]([CH:27]=[CH:28][C:18]=2[N:17]=1)=[CH:25][C:24]1[C:29]2[C:34]([CH2:35][O:36][C:23]=1[CH:22]=3)=[CH:33][C:32]([C:47]1[CH:48]=[CH:49][C:50]3[N:54]=[C:53]([C@@H:55]4[CH2:59][CH2:58][CH2:57][N:56]4[C:60](=[O:70])[C@@H:61]([NH:65][C:66]([O:67][CH3:68])=[O:69])[CH:62]([CH3:63])[CH3:64])[NH:52][C:51]=3[CH:71]=1)=[CH:31][CH:30]=2)=[O:10])([CH3:15])([CH3:13])[CH3:14]

참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 59611353methyl (S)-1-((S)-2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamateHCID 178495650HCID 178495650, 화합물

생성물 1

HCID 178495652HCID 178495652, 화합물

시약·촉매·용매 4

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6228Dimethylformamide용매HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

To a solution of (2S,4S)-tert-butyl 4-(methoxymethyl)-2-(9-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)pyrrolidine-1-carboxylate (400 mg, 0.85 mmol), methyl (S)-1-((S)-2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (360 mg, 0.85 mmol), tetrakis(triphenylphosphine) palladium(0) (38 mg, 0.03 mmol) and dichloro[1,1′-bis(diphenylphosphino) ferrocene]palladium(II) (48 mg, 0.07 mmol) in a mixture of 1,2-dimethoxyethane (8.0 mL) and dimethylformamide (1.4 mL) was added a solution of potassium carbonate (2M in water, 0.98 mL, 1.96 mmol). The resulting mixture was degassed and then heated to 85° C. under argon for 18 hours. After cooling to room temperature, the reaction was diluted with ethyl acetate. The organics were washed with water and brine, dried (Na2SO4), and concentrated. The crude residue was purified by flash chromatography to (2S,4S)-tert-butyl 2-(9-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (156 mg, 29%).

후처리

  1. customThe resulting mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction was diluted with ethyl acetate
  4. washThe organics were washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude residue was purified by flash chromatography to (2S,4S)-tert-butyl 2-(9-(2-((S)-1-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)pyrrolidin-2-yl)-1H-benzo[d]imidazol-6-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl)-4-(methoxymethyl)pyrrolidine-1-carboxylate (156 mg, 29%)

출처 및 근거

ORD 기록
ord-abe2c9fcb6ec45829b77010d8e559c02
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940718B2

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