Triethylamine → 2-(3,5-difluorophenyl)-N-(4-isopropyl-1-oxophthalazin-2(1H)-yl)acetamide

HRID 469518Notes

Reaction equation

HRID 469518 reaction equation
[NH2:1][N:2]1[N:11]=[C:10]([CH:12]([CH3:14])[CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:15].C(N(CC)CC)C.[F:23][C:24]1[CH:25]=[C:26]([CH2:31][C:32](O)=[O:33])[CH:27]=[C:28]([F:30])[CH:29]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C.CCOC(C)=O>[F:23][C:24]1[CH:25]=[C:26]([CH2:31][C:32]([NH:1][N:2]2[N:11]=[C:10]([CH:12]([CH3:13])[CH3:14])[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]2=[O:15])=[O:33])[CH:27]=[C:28]([F:30])[CH:29]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 1454243,5-Difluorophenylacetic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 671616462-amino-4-isopropylphthalazin-1(2H)-one

Product 1

HCID 671622782-(3,5-difluorophenyl)-N-(4-isopropyl-1-oxophthalazin-2(1H)-yl)acetamideYield 32.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of the product of Example 1B (44.5 mg, 0.219 mmol), triethylamine (0.050 mL, 0.36 mmol), 2-(3,5-difluorophenyl)acetic acid (41.0 mg, 0.238 mmol), and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (77.5 mg, 0.241 mmol) in DMF (0.75 mL) was stirred overnight, diluted with EtOAc, washed with 1 N NaOH and brine, dried (Na2SO4), and filtered. The residue was chromatographed on SiO2 (8% EtOAc/CH2Cl2) to give the title compound as a white solid (25.4 mg, 0.071 mmol). 1H NMR (300 MHz, DMSO-d6) δ 11.59 (s, 1H), 8.33 (dd, 1H), 8.16-8.09 (m, 1H), 8.00 (td, 1H), 7.89 (ddd, 1H), 7.19-7.07 (m, 3H), 3.75 (s, 2H), 3.61 (quin, 1H), 1.27 (d, 6H); MS (ESI+) M/Z 357.9 (M+H)+.

Workup

  1. washwashed with 1 N NaOH and brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customThe residue was chromatographed on SiO2 (8% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-f411f0d51f1046d5b0e3077a9bbf3cc2
Source dataset
uspto-grants-2014_01
Patent number
US08629143B2

Reaction notes

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