1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 7-{(2E)-4-[tert-Butyl(methyl)amino]but-2-enoyl}-4-[(3-chloro-4-fluorophenyl)amino]-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile

HRID 38625Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 38625
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([OH:7])=O.[C:8]([NH:12][CH3:13])([CH3:11])([CH3:10])[CH3:9].CCN(C(C)C)C(C)C.[Cl:23][C:24]1[CH:25]=[C:26]([NH:31][C:32]2[C:37]([C:38]#[N:39])=[CH:36][N:35]=[C:34]3[S:40][C:41]4[CH2:42][NH:43][CH2:44][CH2:45][C:46]=4[C:33]=23)[CH:27]=[CH:28][C:29]=1[F:30].CCN=C=NCCCN(C)C>C(Cl)Cl.O>[C:8]([N:12]([CH3:13])[CH2:2]/[CH:3]=[CH:4]/[C:5]([N:43]1[CH2:44][CH2:45][C:46]2[C:33]3[C:34]([S:40][C:41]=2[CH2:42]1)=[N:35][CH:36]=[C:37]([C:38]#[N:39])[C:32]=3[NH:31][C:26]1[CH:27]=[CH:28][C:29]([F:30])=[C:24]([Cl:23])[CH:25]=1)=[O:7])([CH3:11])([CH3:10])[CH3:9]

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531Diisopropylethylamine2×HCID 84552N-Methyl-tert-butylamineHCID 64364114-Bromocrotonic acidHCID 581169284-[(3-Chloro-4-fluorophenyl)amino]-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrile

Produkt 1

HCID 581169547-{(2E)-4-[tert-Butyl(methyl)amino]but-2-enoyl}-4-[(3-chloro-4-fluorophenyl)amino]-5,6,7,8-tetrahydrothieno[2,3-b:5,4-c']dipyridine-3-carbonitrileAusbeute 38,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

(2E)-4-Bromobut-2-enoic acid (100 mg, 0.61 mmol) and tert-butyl methylamine (60 mg, 0.67 mmol) were dissolved in DCM (3.0 mL). DIPEA (94 mg, 0.73 mmol) was added, and the mixture was heated overnight to 50° C. After cooling to rt, the compound of Example 55A (75 mg, 0.21 mmol), DCM (1.0 mL), EDCI (48 mg, 0.25 mmol) and DIPEA (32 mg, 0.25 mmol) were added, and the mixture was stirred at rt overnight. Subsequently, it was diluted with water, and the mixture was extracted three times with DCM. The combined organic layers were dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by preparative HPLC to yield 41 mg (37%) of the title compound.

Aufarbeitung

  1. temperaturethe mixture was heated overnight to 50° C
  2. extractionthe mixture was extracted three times with DCM
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. customthe solvent was removed in vacuo
  5. customThe crude product was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-f403827c0887475ab55fda7d5929c797
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524722B2

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