Phenylacetic Acid → HCID 67161348, compound

HRID 469573Notes

Reaction equation

HRID 469573 reaction equation
[NH2:1][N:2]1[N:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:16].[C:17]1([CH2:23][C:24](O)=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=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>CC(N(C)C)=O>[O:16]=[C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([C:12]([F:15])([F:13])[F:14])=[N:11][N:2]1[NH:1][C:24](=[O:25])[CH2:23][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

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 671611112-amino-4-(trifluoromethyl)phthalazin-1(2H)-one

Product 1

HCID 67161348HCID 67161348, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a 4 mL vial was added the product from Example 11B (20 mg in DMA), 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 [Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm). A gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was used, at a flow rate of 50 mL/min [0-0.5 min 10% A, 0.5-7.0 min linear gradient 10-95% A, 7.0-10.0 min 95% A, 10.0-12.0 min linear gradient 95-10% A]. 1H NMR (500 MHz, DMSO-d6) δ ppm 11.89-11.91 (bs, 1H), 8.43 (dd, J=8.0, 1.3 Hz, 1H), 8.12-8.15 (m, 1H), 7.96-8.08 (m, 2H), 7.32-7.42 (m, 4H), 7.26-7.30 (m, 1H), 3.73 (s, 2H); MS (ESI+) M/Z 348 (M+H)+, 365 (M+NH4)+.

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 [Phenomenex Luna C8(2) 5 um 100 Å AXIA column (30 mm×75 mm)
  6. customwas used, at a flow rate of 50 mL/min [0-0.5 min 10% A, 0.5-7.0 min linear gradient 10-95% A, 7.0-10.0 min 95% A, 10.0-12.0 min linear gradient 95-10% A]

Sources & evidence

ORD record
ord-27d80c080810409da5c9bbc42bafbce0
Source dataset
uspto-grants-2014_01
Patent number
US08629143B2

Reaction notes

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