Diisopropylethylamine → 1-(3-(4-(Pyridin-2-yl)piperazine-1-carbonyl)benzyl)quinazoline-2,4(1H,3H)-dione

HRID 927293Notes

Reaction equation

HRID 927293 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=1)[CH2:7][N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](=[O:18])[NH:10][C:9]1=[O:19])(O)=[O:2].[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>O.CN(C=O)C>[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[N:29]1[CH2:30][CH2:31][N:32]([C:1]([C:4]2[CH:5]=[C:6]([CH:20]=[CH:21][CH:22]=2)[CH2:7][N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11](=[O:18])[NH:10][C:9]2=[O:19])=[O:2])[CH2:33][CH2:34]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 944591-(2-Pyridyl)piperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 683887821-(3-Carboxybenzyl)quinazoline-2,4(1H,3H)-dione

Product 1

HCID 683889351-(3-(4-(Pyridin-2-yl)piperazine-1-carbonyl)benzyl)quinazoline-2,4(1H,3H)-dioneYield 8.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-(3-carboxybenzyl)quinazoline-2,4(1H,3H)-dione (0.2 mmol), 1-(pyridin-2-yl)piperazine (0.2 mmol), 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.26 mmol), N,N-diisopropylethylamine (DIPEA, 0.4 mmol) and DMF (5 mL) were added into a 50 mL two-mouth flask. The obtained mixture was stirred at room temperature for 3 hours. To the mixture was added 50 mL of water and it was extracted by dichloromethane (DCM, 50 mL×2). The organic layer was washed by 1N HCl (50 mL×2) and saturated NaCl aquenous solution (50 mL×2), dried with anhydrous sodium sulphate, and evaporated under reduced pressure to give the crude product. The crude product was purified by column chromatography (ethyl acetate) to give the title compound as white solid (7.7 mg, 8.6% yield). 1H NMR (DMSO-d6): 11.69 (s, 1H), 8.09 (dd, J=5.0 and 1.7 Hz, 1H), 7.99 (dd, J=8.0 and 1.7 Hz, 1H), 7.64 (t, J=7.1 Hz, 1H), 7.53 (t, J=7.8 Hz, 1H), 7.40-7.21 (m, 6H), 6.77 (d, J=8.7 Hz, 1H), 6.64 (dd, J=7.1 and 5.0 Hz, 1H), 5.34 (s, 2H), 3.40-3.20 (m, 8H). MS: m/z 442.3 [M+H]+.

Workup

  1. extractionwas extracted by dichloromethane (DCM, 50 mL×2)
  2. washThe organic layer was washed by 1N HCl (50 mL×2) and saturated NaCl aquenous solution (50 mL×2)
  3. dry with materialdried with anhydrous sodium sulphate
  4. customevaporated under reduced pressure
  5. customto give the crude product
  6. customThe crude product was purified by column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-5bd835c5816a4cfbb107b601bc4d0dfe
Source dataset
uspto-grants-2016_03
Patent number
US09290460B2

Reaction notes

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