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Potassium Carbonate → (S)-tert-butyl 2-(5-(8-chloro-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 1751391
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HRID 1751391 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][C:11](B4OC(C)(C)C(C)(C)O4)=[CH:12][CH:13]=3)[O:8][CH2:7][C:6]=2[CH:24]=1.Br[C:26]1[N:27]=[C:28]([C@@H:31]2[CH2:35][CH2:34][CH2:33][N:32]2[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[NH:29][CH:30]=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]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][C:11]([C:30]4[NH:29][C:28]([C@@H:31]5[CH2:35][CH2:34][CH2:33][N:32]5[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[N:27][CH:26]=4)=[CH:12][CH:13]=3)[O:8][CH2:7][C:6]=2[CH:24]=1
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참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 566051921,1-Dimethylethyl (2S)-2-(5-bromo-1H-imidazol-2-yl)-1-pyrrolidinecarboxylateHCID 696752822-(8-chloro-6H-benzo[c]chromen-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

생성물 1

HCID 69675156(S)-tert-butyl 2-(5-(8-chloro-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate수율 60.9%

시약·촉매·용매 4

HCID 11979704
Tetrakis(triphenylphosphine)palladium
촉매
HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매
HCID 6228Dimethylformamide용매
HCID 80711,2-Dimethoxyethane용매

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온도
85 °C

실험 절차

To a solution of 2-(8-chloro-6H-benzo[c]chromen-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (773 mg, 2.24 mmol), (S)-tert-butyl 2-(4-bromo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (886 mg, 2.8 mmol), tetrakis(triphenylphosphine) palladium(0) (65 mg, 0.05 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (82 mg, 0.11 mmol) in a mixture of 1,2-dimethoxyethane (10.0 mL) and dimethylformamide (2 mL) was added a solution of potassium carbonate (2M in water, 3.5 mL, 7.0 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 yield (S)-tert-butyl 2-(5-(8-chloro-6H-benzo[c]chromen-3-yl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (617 mg, 50%). LCMS-ESI+: calculated for C25H26ClN3O3: 451.96; observed [M+1]+: 452.53.

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

출처 및 근거

ORD 기록
ord-2ddc4750f2444b9a8dbaa9c54ebfa928
출처 데이터셋
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09156823B2

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