Diisopropylethylamine → 4-(4-fluoro-3-(4-(2-oxo-2-(piperidin-1-yl)ethoxy)piperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

HRID 1091793Notes

Reaction equation

HRID 1091793 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[N:56]1([C:62](=[O:71])[CH2:63][O:64][CH:65]2[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]2)[CH2:61][CH2:60][CH2:59][CH2:58][CH2:57]1>CC(N(C)C)=O>[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1[C:4]([N:68]1[CH2:69][CH2:70][CH:65]([O:64][CH2:63][C:62](=[O:71])[N:56]2[CH2:57][CH2:58][CH2:59][CH2:60][CH2:61]2)[CH2:66][CH2:67]1)=[O:6]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 242088381-[(Piperidin-4-yloxy)acetyl]piperidineHCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acid

Product 1

HCID 577917714-(4-fluoro-3-(4-(2-oxo-2-(piperidin-1-yl)ethoxy)piperidine-1-carbonyl)benzyl)phthalazin-1(2H)-oneYield 89.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid (1) (0.20 g, 0.67 mmol) and HBTU (0.381 g, 1.01 mmol) were added to DMA (4 mL), to this was added N-ethyl-N-isopropylpropan-2-amine (0.179 mL, 1.01 mmol) and then 1-(piperidin-1-yl)-2-(piperidin-4-yloxy)ethanone (112) (0.152 g, 0.67 mmol). The reaction was stirred for 2 hours before being evaporated to dryness and purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the desired material (0.303 g, 89% yield); 1H NMR (400.132 MHz, DMSO) δ 1.07-1.39 (8H, m), 1.46-1.56 (1H, m), 1.61-1.71 (1H, m), 2.76-2.85 (1H, m), 3.02-3.09 (2H, m), 3.10-3.20 (4H, m), 3.34-3.41 (1H, m), 3.66-3.75 (1H, m), 3.90-3.93 (2H, m), 4.08-4.12 (2H, m), 6.99 (1H, t), 7.09-7.21 (2H, m), 7.57-7.69 (1H, m), 7.72-7.76 (1H, m), 8.02-8.06 (2H, m), 12.34 (1H, s); m/z (LC-MS, ESI+), RT=1.76 (M+H 507.5).

Workup

  1. custombefore being evaporated to dryness
  2. custompurified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  3. additionFractions containing the desired compound
  4. customwere evaporated to dryness

Sources & evidence

ORD record
ord-0456e4aa719846bc97de1ce91e9d731b
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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