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1,3-Dioxolane-4-methanamine, 2,2-dimethyl- → N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2ylmethyl)amino)phthalazin-1-yl)nicotinamide

HRID 593707
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 593707
[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[N:10][N:11]=[C:12]3[C:17]2[CH:18]=[N:19][CH:20]=[C:21]([CH:25]=2)[C:22]([OH:24])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:58][C:59]1([CH3:66])[O:63][CH:62]([CH2:64][NH2:65])[CH2:61][O:60]1>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:58][C:59]1([CH3:66])[O:63][CH:62]([CH2:64][NH:65][C:22](=[O:24])[C:21]2[CH:25]=[C:17]([C:12]3[C:13]4[C:8](=[C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[CH:16]=[CH:15][CH:14]=4)[C:9]([NH:26][CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[N:10][N:11]=3)[CH:18]=[N:19][CH:20]=2)[CH2:61][O:60]1
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Komponenten

6

Edukt 3

HCID 41223491,3-Dioxolane-4-methanamine, 2,2-dimethyl-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 904238795-(5-Phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinic acid

Produkt 1

HCID 86270294N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2ylmethyl)amino)phthalazin-1-yl)nicotinamide
Ausbeute 11,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)phthalazin-1-yl)nicotinic acid (0.200 g, 0.461 mmol) in DMF (5 mL) was added HATU (0.526 g, 1.38 mmol) at ambient temperature. DMAP (0.169 g, 1.38 mmol) was added followed by (2,2-dimethyl-1,3-dioxolan-4-yl)methanamine (0.0610 g, 0.461 mmol, commercial) and the contents were stirred at ambient temperature for 16 h. The reaction mixture was concentrated under reduced pressure and the residue was diluted with water. The reaction mixture was extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by combiflash (REDISEP®, silica gel, 12 g, 50% EtOAc/hexanes) to obtain N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino) phthalazin-1-yl)nicotinamide (0.0300 g, 11.9%) as an off-white solid. LCMS (Condition 7): retention time 1.76 min, [M+1]=547.2. HPLC (Condition 24): retention time 7.68 min, Purity 96.10%. 1H NMR (400 MHz, DMSO-d6) δ 1.27 (s, 3H), 1.36 (s, 3 H), 3.31-3.51 (m, 2 H), 3.74 (dd, J=5.6 Hz, J=8.4 Hz, 1 H), 4.03 (dd, J=6.0 Hz, J=8.4 Hz, 1 H), 4.26 (m, 1 H), 4.66 (d, J=4.0 Hz, 2 H), 6.33 (dd, J=4.0 Hz, J=4.4 Hz, 1 H), 7.22 (dd, J=5.2 Hz, J=6.4 Hz, 1 H), 7.29 (d, J=6.8 Hz, 1 H), 7.50-7.59 (m, 5 H), 7.69-7.73 (m, 2 H), 7.84 (dd, J=1.6 Hz, J=8.0 Hz, 1 H), 7.93 (dd, J=7.2 Hz, J=8.0 Hz, 1 H), 8.23 (d, J=4.8 Hz, 1 H), 8.51 (t, J=2.0 Hz, 1 H), 8.94 (dd, J=5.6 Hz, J=6.0 Hz, 1 H), 9.0 (d, J=2.0 Hz, 1H), 9.16 (d, J=2.0 Hz, 1 H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with water
  3. extractionThe reaction mixture was extracted with EtOAc
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by combiflash (REDISEP®, silica gel, 12 g, 50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c8f27ea3baaa4b4f89549f040128ce75
Quelldatensatz
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09242966B2

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