Diisopropylamine → ((S)-1-Cyclohexyl-2-{(S)-2-[2-(2,3-dihydro-indol-1-yl)-pyridin-4-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl ester

HRID 1667619Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1667619
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:53]1[CH2:57][CH2:56][CH2:55][C@H:54]1[C:58]1[CH:63]=[CH:62][N:61]=[C:60]([N:64]2[C:72]3[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=3)[CH2:66][CH2:65]2)[CH:59]=1.C(NC(C)C)(C)C>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([N:53]1[CH2:57][CH2:56][CH2:55][C@H:54]1[C:58]1[CH:63]=[CH:62][N:61]=[C:60]([N:64]2[C:72]3[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=3)[CH2:66][CH2:65]2)[CH:59]=1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

Komponenten

8

Edukt 5

HCID 7912DiisopropylamineHCID 757711-HydroxybenzotriazoleHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 581119321-((S)-4-pyrrolidin-2-yl-pyridin-2-yl)-2,3-dihydro-1H-indole

Produkt 1

HCID 66889172((S)-1-Cyclohexyl-2-{(S)-2-[2-(2,3-dihydro-indol-1-yl)-pyridin-4-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl esterAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A solution of (S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid (99 mg, 0.39 mmol), HOBt (57 mg, 0.42 mmol) and HBTU (160 mg, 0.42 mmol) in DMF (10 mL) is stirred at room temperature for 30 min. Then a solution of 1-((S)-4-pyrrolidin-2-yl-pyridin-2-yl)-2,3-dihydro-1H-indole (6) in DMF (10 mL) is added, followed by diisopropylamine (226 mg, 1.75 mmol). After stirring at room temperature for 2 h, the reaction mixture is diluted with water and extracted with EtOAc. The combined organic layers are washed with water, sat. NaHCO3, brine, dried over Na2SO4, filtered and concentrated down. The crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜40%) to give ((S)-1-Cyclohexyl-2-{(S)-2-[2-(2,3-dihydro-indol-1-yl)-pyridin-4-yl]-pyrrolidin-1-yl}-2-oxo-ethyl)-carbamic acid tert-butyl ester as white solid (120 mg, 68%). M/Z=505.3 [M+1]

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe combined organic layers are washed with water, sat. NaHCO3, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated down
  6. customThe crude product is purified by flash chromatography on silica gel (EtOAc/Hexane: 5%˜40%)

Quellen und Nachweise

ORD-Eintrag
ord-ff5c1cc04cb443eea9d63bc7bbdc24de
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08044209B2

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