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 593707Notes

Reaction equation

HRID 593707 reaction equation
[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

Participants

6

Reactant 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

Product 1

HCID 86270294N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-5-(5-phenyl-4-((pyridin-2ylmethyl)amino)phthalazin-1-yl)nicotinamideYield 11.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-c8f27ea3baaa4b4f89549f040128ce75
Source dataset
uspto-grants-2016_01
Patent number
US09242966B2

Reaction notes

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