Phenylacetic Acid → N-[4-(morpholin-4-yl)-1-oxophthalazin-2(1H)-yl]-2-phenylacetamide

HRID 535539

Reaction equation

HRID 535539 reaction equation
[NH2:1][N:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:18].[C:19]1([CH2:25][C:26](O)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C>>[N:12]1([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3](=[O:18])[N:2]([NH:1][C:26](=[O:27])[CH2:25][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:11]=2)[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

5

Reactant 4

HCID 999Phenylacetic AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 709761042-amino-4-morpholinophthalazin-1(2H)-one

Product 1

HCID 70976253N-[4-(morpholin-4-yl)-1-oxophthalazin-2(1H)-yl]-2-phenylacetamide

Procedure

To a 4 mL vial was added the product from Example 1B (20 mg in dimethyl acetamide), phenylacetic acid [1.5 equivalents in dimethyl acetamide], O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 2 equivalents in dimethyl acetamide) and triethylamine (3 equivalents, neat). The vial was capped and microwaved at 150° C. for 30 minutes. The reaction was checked by LC/MS and concentrated to dryness upon completion. The residue was dissolved in 1:1 MeOH:DMSO and purified by reverse phase HPLC (conditions from Example 10C): 1H NMR (500 MHz, DMSO-d6/D2O) δ 8.33-8.28 (m, 1H), 8.03 (d, J=7.5, 1H), 8.01-7.96 (m, 1H), 7.94-7.87 (m, 1H), 7.40-7.33 (m, 4H), 7.33-7.25 (m, 1H), 3.86-3.78 (m, 4H), 3.67 (s, 2H), 3.11-3.06 (m, 4H); MS (ESI+) M/Z 365 (M+H)+.

Workup

  1. customThe vial was capped
  2. custommicrowaved at 150° C. for 30 minutes
  3. concentrationconcentrated to dryness upon completion
  4. dissolutionThe residue was dissolved in 1:1 MeOH
  5. customDMSO and purified by reverse phase HPLC (conditions from Example 10C)

Sources & evidence

ORD record
ord-18bf992b4f04433fac641294f2b4bc7e
Source dataset
uspto-grants-2014_10
Patent number
US08859549B2

Linked notes

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