1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-N-(3-fluoro-4-(2-(4-(3-hydroxypyrrolidine-1-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

HRID 1676369Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676369
[F:1][C:2]1[CH:26]=[C:25]([NH:27][C:28]([C:30]2[C:35](=[O:36])[N:34]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:33]=[CH:32][CH:31]=2)=[O:29])[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=3)[S:13][C:6]=12.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.[NH:66]1[CH2:70][CH2:69][C@@H:68]([OH:71])[CH2:67]1.CCN(C(C)C)C(C)C>O.CN(C=O)C>[F:1][C:2]1[CH:26]=[C:25]([NH:27][C:28]([C:30]2[C:35](=[O:36])[N:34]([C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)[N:33]=[CH:32][CH:31]=2)=[O:29])[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([N:66]4[CH2:70][CH2:69][C@@H:68]([OH:71])[CH2:67]4)=[O:20])=[CH:21][CH:22]=3)[S:13][C:6]=12

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 2759337(R)-3-PyrrolidinolHCID 27960291-Hydroxybenzotriazole hydrateHCID 673452974-(7-(2-Fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)benzoic acid

Produkt 1

HCID 58949446(R)-N-(3-fluoro-4-(2-(4-(3-hydroxypyrrolidine-1-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamideAusbeute 55,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A capped vial was charged with 4-(7-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)benzoic acid (0.100 g, 0.168 mmol), HOBT-H2O (0.103 g, 0.671 mmol), EDCI (0.129 g, 0.671 mmol), and DMF (2 mL). After stirring for 45 minutes, (R)-pyrrolidin-3-ol (0.0584 g, 0.671 mmol) and Hunig's base (0.175 ml, 1.01 mmol) were added. After stirring for 18 hours, water (20 mL) was added. The formed precipitate was isolated by filtration. After drying, (62 mg, 55%) of product was isolated as orange solid. LRMS (esi+) 666 m/z (M+1) detected. 1H NMR (CDCl3, 400 MHz) δ 11.84 (s, 1H), 8.47 (s, 1H), 8.39 (d, J=4 Hz, 1H), 8.22 (d, J=4 Hz, 1H), 7.97 (m, 1H), 7.76 (m, 3H), 7.62 (m, 4H), 7.39 (d, J=9 Hz, 1H), 7.26 (m, 3H), 6.52 (d, J=6 Hz, 1H), 4.50 (br s, 1H), 3.72 (m, 5H), 2.07 (m, 2H).

Aufarbeitung

  1. stirringAfter stirring for 18 hours
  2. customThe formed precipitate was isolated by filtration
  3. customAfter drying

Quellen und Nachweise

ORD-Eintrag
ord-12b2d4f226cc423099a7a359a47deaa5
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003662B2

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