4-Methylmorpholine → N-(1-{5-[(2,5-dimethyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]pyridin-2-yl}piperidin-4-yl)-6-(3-fluorophenyl)nicotinamide

HRID 602091Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 602091
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:17]1[C:22]2[CH2:23][CH2:24][O:25][CH2:26][C:21]=2[CH:20]=[N:19][C:18]=1[N:27]1[CH2:32][CH2:31][CH:30]([NH2:33])[CH2:29][CH2:28]1.CCN=C=NCCCN(C)C.[CH:45]1[CH:46]=[CH:47][C:48]2[N:53](O)N=N[C:49]=2[CH:50]=1.CN1CCOCC1>O.CC(N(C)C)=O>[N:17]1[C:22]2[CH2:23][CH2:24][O:25][CH2:26][C:21]=2[CH:20]=[N:19][C:18]=1[N:27]1[CH2:32][CH2:31][CH:30]([NH:33][C:12](=[O:14])[C:11]2[CH:15]=[CH:16][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)[CH2:29][CH2:28]1.[CH3:47][CH:48]1[CH:49]=[CH:50][CH:45]([CH3:46])[N:53]1[C:26]([C:21]1[CH:22]=[CH:23][C:18]([N:27]2[CH2:28][CH2:29][CH:30]([NH:33][C:12](=[O:14])[C:11]3[CH:15]=[CH:16][C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=4)=[N:9][CH:10]=3)[CH2:31][CH2:32]2)=[N:19][CH:20]=1)=[O:25]

Komponenten

9

Edukt 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 247299726-(3-Fluorophenyl)nicotinic acidHCID 670066751-(7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)piperidin-4-amine

Produkt 2

HCID 59743688N-[1-(7,8-Dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)piperidin-4-yl]-6-(3-fluorophenyl)nicotinamideHCID 67267283N-(1-{5-[(2,5-dimethyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]pyridin-2-yl}piperidin-4-yl)-6-(3-fluorophenyl)nicotinamideAusbeute 154,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

To a vial was added, 6-(3-fluorophenyl)nicotinic acid (46.4 mg, 0.213 mmol), 1-(7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-yl)piperidin-4-amine (50 mg, 0.21 mmol), EDAC (45.0 mg, 0.235 mmol), HOBT (28.8 mg, 0.213 mmol), and DMA (1 mL) followed by NMM (0.058 mL, 0.534 mmol). The reaction was stirred overnight at room temperature and then diluted with H2O and the resulting solid filtered and collected to give the desired product, N-(1-{5-[(2,5-dimethyl-2,5-dihydro-1H-pyrrol-1-yl)carbonyl]pyridin-2-yl}piperidin-4-yl)-6-(3-fluorophenyl)nicotinamide (81 mg, 88%). 1H NMR (400 MHz, DMSO-d6) □ ppm 9.06 (1H, s), 8.45 (1H, d, J=7.5 Hz), 8.21-8.30 (1H, m), 8.04-8.14 (2H, m), 7.89-8.02 (2H, m) 7.49-7.59 (1H, m), 7.29 (1H, t), 4.49-4.64 (5H, m), 4.11 (1H, br. s.), 3.89 (2H, t, J=5.9 Hz), 2.94-3.07 (2 H, m), 1.88 (2H, d, J=10.1 Hz), 1.42-1.56 (3H, m). HRMS (TOF, ES+) calculated for M+H: 434.1992; observed 434.2165.

Aufarbeitung

  1. additionTo a vial was added
  2. filtrationthe resulting solid filtered
  3. customcollected

Quellen und Nachweise

ORD-Eintrag
ord-8ea38fdfeafe4f70a337c3e7e2eaa897
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902373B2

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