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Potassium Carbonate → (3-{(S)-5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 2046560
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2046560
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]3([C:23](O)=[O:24])[CH2:22][O:21][CH2:20]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[Cl:49][C:50]1[CH:51]=[C:52]([F:72])[C:53]([C:66]2[N:70]=[C:69]([CH3:71])[O:68][N:67]=2)=[C:54]([C:56]2[CH:57]=[C:58]3[C:62](=[CH:63][CH:64]=2)[C@@H:61]([NH2:65])[CH2:60][CH2:59]3)[CH:55]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:17])[NH:18][C:19]3([C:23](=[O:24])[NH:65][C@@H:61]4[C:62]5[C:58](=[CH:57][C:56]([C:54]6[CH:55]=[C:50]([Cl:49])[CH:51]=[C:52]([F:72])[C:53]=6[C:66]6[N:70]=[C:69]([CH3:71])[O:68][N:67]=6)=[CH:64][CH:63]=5)[CH2:59][CH2:60]4)[CH2:22][O:21][CH2:20]3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 11430Potassium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 679511683-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)oxetane-3-carboxylic acidHCID 68296736(S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylamine

Produkt 1

HCID 68296802(3-{(S)-5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylcarbamoyl}-oxetan-3-yl)-carbamic acid 9H-fluoren-9-ylmethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a solution of 3-(9H-fluoren-9-ylmethoxycarbonylamino)-oxetane-3-carboxylic acid (1.70 g, 5.01 mmol) in dry DMF (50.0 ml) were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.60 g, 8.35 mmol) and 1-hydroxybenzotriazole hydrate (0.95 g, 6.20 mmol) at room temperature. The resulting colorless solution was stirred for 10 min before a solution of (S)-5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-indan-1-ylamine (1.64 g, 4.77 mmol, intermediate A-11) in dry DMF (2.0 ml) was added. This mixture was stirred at room temperature for 20 h. Then water was added, the pH was adjusted to 9 with sat. K2CO3 solution and the mixture was extracted twice with MeCl2. The combined organic layers were washed with water and brine, dried with MgSO4 and evaporated. The remaining light brown foam was purified by chromatography (silica gel; MeCl2/MeOH 100:0 to 98:2%) and the title compound was obtained as off white foam (3.17 g, 100%). MS: 665.2 (MH+, 1Cl).

Aufarbeitung

  1. additionwas added
  2. extractionthe mixture was extracted twice with MeCl2
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried with MgSO4
  5. customevaporated
  6. customThe remaining light brown foam was purified by chromatography (silica gel; MeCl2/MeOH 100:0 to 98:2%)

Quellen und Nachweise

ORD-Eintrag
ord-93dc9868eda341a28ede523e866941ba
Quelldatensatz
uspto-grants-2013_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08592426B2

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