Diisopropylethylamine → [(3R,4S)-3-[(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-(5-chloro-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanone

HRID 906937Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 906937
[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][CH2:7][C@@H:8]([C@@H:17]1[C@@H:21]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:20][NH:19][CH2:18]1)[O:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:65][C:66]1[N:71]=[N:70][CH:69]=[C:68]([C:72](O)=[O:73])[CH:67]=1>CN(C=O)C.C(OCC)(=O)C>[C:1]([Si:5]([CH3:31])([CH3:30])[O:6][CH2:7][C@@H:8]([C@@H:17]1[C@@H:21]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:20][N:19]([C:72]([C:68]2[CH:67]=[C:66]([CH3:65])[N:71]=[N:70][CH:69]=2)=[O:73])[CH2:18]1)[O:9][C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 553007686-Methyl-4-pyridazinecarboxylic acid hydrochlorideHCID 671315312-{(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine

Produkt 1

HCID 67131632[(3R,4S)-3-[(R)-2-(tert-Butyl-dimethyl-silanyloxy)-1-(5-chloro-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidin-1-yl]-(6-methyl-pyridazin-4-yl)-methanoneAusbeute 27,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 2-{(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-[(3R,4S)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-5-chloro-pyridine (220 mg) in DMF (12 mL)at −20° C. were added Hunig base (0.132 mL, 0.78 mmol) and then HATU (202 mg) and then 6-methyl-pyridazine-4-carboxylic acid (0.78 mmol, described herein above). The mixture was diluted with ethyl acetate and washed with aq.ammonium chloride solution three times and aq. sodium bicarbonate solution. The separated organic phase was dried over sodium sulfate and concentrated in vaccuo after filtration. The residue was purified by TLC (SiO2, MeOH/DCM, 1:10) yielded 74 mg (27%) of the title compound as a light yellow oil. ES-MS m/e: 623.3 (M+H+).

Aufarbeitung

  1. washwashed with aq
  2. dry with materialThe separated organic phase was dried over sodium sulfate
  3. concentrationconcentrated in vaccuo
  4. filtrationafter filtration
  5. customThe residue was purified by TLC (SiO2, MeOH/DCM, 1:10)

Quellen und Nachweise

ORD-Eintrag
ord-41deab3745d34fd8adfe49badc077ce0
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08012998B2

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