Dichloromethane → HCID 76604934, Verbindung

HRID 2405830Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2405830
C(OC(=O)[NH:7][CH:8]([C:13]([N:15]1[CH2:19][CH:18]([O:20][C:21]2[C:30]3[C:25](=C(Cl)[CH:27]=[CH:28][CH:29]=3)[N:24]=[C:23]([O:32][CH2:33][CH:34]([O:37][CH3:38])[O:35][CH3:36])[CH:22]=2)[CH2:17][CH:16]1[C:39](=[O:57])[NH:40][C:41]1([C:46]([NH:48][S:49]([O:52][C:53]2([CH3:56])[CH2:55][CH2:54]2)(=[O:51])=[O:50])=[O:47])[CH2:43][CH:42]1[CH2:44][CH3:45])=[O:14])[C:9]([CH3:12])([CH3:11])[CH3:10])(C)(C)C.C(O)(C(F)(F)F)=O.[F:66][C:67]([F:85])([F:84])[C:68]([O:71][C:72](=[O:83])OC1C=CC([N+]([O-])=O)=CC=1)([CH3:70])[CH3:69].C(N(C(C)C)CC)(C)C.[CH2:95]([Cl:97])Cl>CO>[F:85][C:67]([F:66])([F:84])[C:68]([O:71][C:72](=[O:83])[NH:7][CH:8]([C:13]([N:15]1[CH2:19][CH:18]([O:20][C:21]2[C:30]3[C:25](=[C:95]([Cl:97])[CH:27]=[CH:28][CH:29]=3)[N:24]=[C:23]([O:32][CH2:33][CH:34]([O:35][CH3:36])[O:37][CH3:38])[CH:22]=2)[CH2:17][CH:16]1[C:39](=[O:57])[NH:40][C:41]1([C:46]([NH:48][S:49]([O:52][C:53]2([CH3:56])[CH2:54][CH2:55]2)(=[O:50])=[O:51])=[O:47])[CH2:43][CH:42]1[CH2:44][CH3:45])=[O:14])[C:9]([CH3:10])([CH3:11])[CH3:12])([CH3:69])[CH3:70]

Komponenten

7

Edukt 5

HCID 6344Dichloromethane2×HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 577851834-Nitrophenyl 1,1,1-Trifluoro-2-Methylpropan-2-yl-carbonateHCID 76605053(1-{4-[8-Chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid tert-butyl ester

Produkt 1

HCID 76604934HCID 76604934, VerbindungAusbeute 47 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Versuchsvorschrift

(1-{4-[8-chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid tert-butyl ester (444 mg, 0.520 mmol) was dissolved in CH2Cl2 (2.6 mL) and MeOH (0.21 mL, 5.20 mmol), and treated with TFA (2.6 mL). After stirring for 25 min at room temperature, MeOH (7 mL) was added and the solvents were removed in vacuo. The crude mixture was partitioned with saturated NaHCO3 and DCM. The layers were separated and the organic layer was dried over Na2SO4 and concentrated. The resultant residue was dissolved in DCM (5.2 mL) to which carbonic acid 4-nitro-phenyl ester 2,2,2-trifluoro-1,1-dimethyl-ethyl ester (183 mg, 0.624 mmol) and diisopropylethylamine (362 μL, 2.08 mmol) were added sequentially. After stirring for 24 h at 35° C., the reaction was purified by column chromatography on silica (3-7% MeOH/DCM) to provide (1-{4-[8-chloro-2-(2,2-dimethoxy-ethoxy)-quinolin-4-yloxy]-2-[2-ethyl-1-(1-methyl-cyclopropoxysulfonylaminocarbonyl)-cyclopropylcarbamoyl]-pyrrolidine-1-carbonyl}-2,2-dimethyl-propyl)-carbamic acid 2,2,2-trifluoro-1,1-dimethyl-ethyl ester (222 mg, 47% yield). LCMS found 908.0 [M+H]+.

Aufarbeitung

  1. customthe solvents were removed in vacuo
  2. customThe crude mixture was partitioned with saturated NaHCO3 and DCM
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. additionwere added sequentially
  7. stirringAfter stirring for 24 h at 35° C.
  8. customthe reaction was purified by column chromatography on silica (3-7% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-687829066e6b4db984595a370cae526e
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08809267B2

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