Diisopropylethylamine → 1-(3-(4-(Pyrimidin-2-yl)piperazine-1-carbonyl)benzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione

HRID 512124Notes

Reaction equation

HRID 512124 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[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=2[C:11](=[O:18])[NH:10][C:9]1=[O:19])(O)=[O:2].[N:23]1[CH:28]=[CH:27][CH:26]=[N: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>CN(C=O)C.O>[N:23]1[CH:28]=[CH:27][CH:26]=[N:25][C:24]=1[N:29]1[CH2:34][CH2:33][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[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=3[C:11](=[O:18])[NH:10][C:9]2=[O:19])=[O:2])[CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 887471-(2-Pyrimidinyl)piperazineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89545385HCID 89545385, compound

Product 1

HCID 715521911-(3-(4-(Pyrimidin-2-yl)piperazine-1-carbonyl)benzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dioneYield 23.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(3-carboxybenzyl)-5,6,7,8-tetrahydroquinazoline-2,4(1H,3H)-dione (0.2 mmol), 1-(pyrimidin-2-yl)piperazine (0.2 mmol), 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.26 mmol) and N,N-diisopropylethylamine (DIPEA, 0.4 mmol) in DMF (5 mL) was stirred at room temperature overnight. To the mixture was added 50 mL of water and it was extracted with EA (50 mL×3). The organic layer was washed by 1 N hydrochloric acid (50 mL×1) and saturated NaCl aquenous solution (50 mL×1), dried with anhydrous sodium sulfate, and concentrated to give the crude product, which was purified by flash chromatography (DCM: MeOH=20:1) to give the title compound (20.43 mg, 23.3% yield) as white solid. 1H NMR (DMSO-d6): 11.35 (s, 1H), 8.39 (d, J=4.5 Hz, 2H), 7.48-7.41 (m, 1H), 7.36-7.24 (m, 3H), 6.67 (t, J=4.8 Hz, 1H), 5.10 (s, 2H), 3.88-3.20 (m, 8H), 2.46-2.42 (m, 2H), 2.25-2.21 (m, 2H), 1.69-1.43 (m, 4H). MS: m/z 447.4 [M+H]+.

Workup

  1. extractionwas extracted with EA (50 mL×3)
  2. washThe organic layer was washed by 1 N hydrochloric acid (50 mL×1) and saturated NaCl aquenous solution (50 mL×1)
  3. dry with materialdried with anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by flash chromatography (DCM: MeOH=20:1)

Sources & evidence

ORD record
ord-02e31e72d2974c709a0609fdb05f4e43
Source dataset
uspto-grants-2015_08
Patent number
US09102631B2

Reaction notes

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