Nicotinic Acid → HCID 178493884, Verbindung

HRID 339783Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 339783
[OH:1][C@H:2]([CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[N:10]([CH2:18][CH2:19][N:20]=3)[C:11]([NH2:17])=[N:12][C:13]=2[C:14]=1[O:15][CH3:16].[C:28](O)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(CC1C=C(CN(C)C)C(O)=C(CN(C)C)C=1)C>[OH:1][C@H:2]([CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1)[CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[N:10]([CH2:18][CH2:19][N:20]=3)[C:11]([NH:17][C:28]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=3)=[O:35])=[N:12][C:13]=2[C:14]=1[O:15][CH3:16]

Komponenten

6

Edukt 4

HCID 938Nicotinic AcidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 178493885(2R)-1-[(5-amino-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)oxy]-3-piperidin-1-ylpropan-2-ol

Produkt 1

HCID 178493884HCID 178493884, VerbindungAusbeute 67,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 70262,4,6-Tris((dimethylamino)methyl)phenolLösungsmittel

Versuchsvorschrift

To a slurry of N-(8-{[(2R)-2-hydroxy-3-(piperidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)amine (0.125 g, 0.34 mmol) and nicotinic acid (0.052 g, 0.42 mmol, 1.3 equiv.) in DMF 3.6 mL) was added PyBOP (0.218 g, 0.42 mmol, 1.3 equiv.) followed by diisopropylethylamine (0.23 mL, 1.34 mmol, 4.0 equiv.). The resulting mixture was stirred at room temperature. After a few hours the mixture turned to a clear solution. The resulting solids were removed by filtration, washed sequentially with DMF, water, then MeOH, and dried at 50° C. under reduced pressure to afford N-(8-{[(2R)-2-hydroxy-3-(piperidin-1-yl)propyl]oxy}-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide (0.11 g, 66%): HPLC ret. time 1.00 min.; 1H NMR (DMSO-d6+1 drop TFA-d) δ 1.30, 1.44 m, 1H), 1.58-1.71 (m, 2H), 1.72-1.85 (m, 3H), 2.89-3.56 (m, 2H), 3.18 (dd, J=10.1, 13.1 Hz, 1H), 3.25-3.31 (m, 1H), 3.45-3.52 (m, 2H), 4.03 (s, 3H), 4.20-4.29 (m, 4H), 4.38-4.49 (m, 1H), 4.53-4.60 (m, 2H), 7.48 (d, J=9.4 Hz, 1H), 7.85 (dd, J=5.3, 7.9 Hz, 1H), 8.04 (d, J=9.1 Hz, 1H), 8.82 (br d, J=8.1 Hz, 1H), 8.93 (dd, J=1.5, 5.3 Hz, 1H), 9.47 (d, J=1.5 Hz, 1H); mass spectrum m/z 479 ((M+1)+, 0.4%).

Aufarbeitung

  1. waitAfter a few hours the mixture turned to a clear solution
  2. customThe resulting solids were removed by filtration
  3. washwashed sequentially with DMF, water
  4. dry with materialMeOH, and dried at 50° C. under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-1d8e9aa45ce1419e92c735cdfa9269fd
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895549B2

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