tert-butyl N-(5-(tributylstannyl)-1,3-thiazol-2-yl)carbamate → tert-Butyl (5-(6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)-1,3-thiazol-2-yl)carbamate

HRID 2092872

Reaktionsgleichung

Reaktionsgleichung von HRID 2092872
Cl[C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]2[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=1.C([Sn](CCCC)(CCCC)[C:44]1[S:48][C:47]([NH:49][C:50](=[O:56])[O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[N:46][CH:45]=1)CCC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:34]([O:33][C:32]([NH:31][C@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][C@H:25]1[NH:24][C:4]1[N:3]=[C:2]([C:44]2[S:48][C:47]([NH:49][C:50](=[O:56])[O:51][C:52]([CH3:54])([CH3:53])[CH3:55])=[N:46][CH:45]=2)[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]=1[F:23])=[O:38])([CH3:35])([CH3:36])[CH3:37]

Komponenten

5

Edukt 2

HCID 2763269tert-butyl N-(5-(tributylstannyl)-1,3-thiazol-2-yl)carbamateHCID 86654712tert-Butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

Produkt 1

HCID 86654741tert-Butyl (5-(6-(((1R,2S)-2-((tert-butoxycarbonyl)amino)cyclohexyl)amino)-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)-1,3-thiazol-2-yl)carbamateAusbeute 64,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 1140TolueneLösungsmittel

Versuchsvorschrift

A solution of tert-butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (50 mg, 0.091 mmol), tert-butyl 5-(tributylstannyl)thiazol-2-ylcarbamate (53.5 mg, 0.109 mmol), and tetrakis(triphenylphosphine)palladium(0) (105 mg, 0.091 mmol) in toluene (1 mL) was heated to 102° C. for 24 h. After removal of the solvent, the resulting crude material was reconstituted in MeOH/DMF (6.0 mL) and purified via preparative HPLC eluting with water (0.05% TFA) and ACN (70-75% gradient, 0.035% TFA). The collected fractions were stripped to dryness via rotary evaporation to yield the title compound (42 mg, 64%). [M+H] calc'd for C35H45FN6O7S, 713. found, 713.

Aufarbeitung

  1. customAfter removal of the solvent
  2. custompurified via preparative HPLC
  3. washeluting with water (0.05% TFA) and ACN (70-75% gradient, 0.035% TFA)
  4. customThe collected fractions were stripped to dryness via rotary evaporation

Quellen und Nachweise

ORD-Eintrag
ord-96a626f880e64391b0ee9d3f11787586
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440689B2

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