(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamide → {4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 605061Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 605061
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:42])[NH:17][C:18]3[CH:23]=[CH:22][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:40])[NH:32][C:33]5[CH:38]=[CH:37][C:36]([Br:39])=[CH:35][N:34]=5)=[CH:27][C:26]=4[NH2:41])=[CH:20][CH:19]=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.C([C:45]1[C:46]([N:54]=[CH:55][N:56]([CH3:58])C)=[N:47][C:48]([CH:51]([CH3:53])[CH3:52])=[CH:49][CH:50]=1)#N>C(O)(=O)C>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:42])[NH:17][C:18]3[CH:19]=[CH:20][C:21]([S:24][C:25]4[CH:30]=[CH:29][C:28]([C:31](=[O:40])[NH:32][C:33]5[CH:38]=[CH:37][C:36]([Br:39])=[CH:35][N:34]=5)=[CH:27][C:26]=4[NH:41][C:58]4[C:45]5[CH:50]=[CH:49][C:48]([CH:51]([CH3:52])[CH3:53])=[N:47][C:46]=5[N:54]=[CH:55][N:56]=4)=[CH:22][CH:23]=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

Komponenten

4

Edukt 2

HCID 66808369(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamideHCID 67040714{4-[2-Amino-4-(5-bromo-pyridin-2-ylcarbamoyl)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl ester

Produkt 1

HCID 67040609{4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 9H-fluoren-9-ylmethyl esterAusbeute 58,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of the product from Example 17D (23.9 g, 37.4 mmol) and N′-(3-cyano-6-isopropyl-pyridin-2-yl)-N,N-dimethyl-formamidine (9.71 g, 44.9 mmol, 1.2 eq) in 450 mL of glacial acetic acid was heated in an oil bath at 150° C. for 2 h and then cooled to room temperature. The reaction mixture was evaporated in vacuo and the residue was dissolved in approximately 70 mL of dichloromethane. This material was purified by silica gel chromatography using a Biotage Flash 75M cartridge, eluting first with 1:4 ethyl acetate/dichloromethane followed by 98:2 dichloromethane/methanol. The resulting product triturated with dichloromethane and filtered to provide the title compound as a white solid (17.6 g, 58%).

Aufarbeitung

  1. temperaturecooled to room temperature
  2. customThe reaction mixture was evaporated in vacuo
  3. dissolutionthe residue was dissolved in approximately 70 mL of dichloromethane
  4. customThis material was purified by silica gel chromatography
  5. washeluting first with 1:4 ethyl acetate/dichloromethane
  6. customThe resulting product triturated with dichloromethane
  7. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-2fa67cb2020146cb9cc6dbc01988a0b8
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07910595B2

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