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

HRID 1091790Notes

Reaction equation

HRID 1091790 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](O)=[O:5].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.[NH:56]1[CH2:61][CH2:60][CH:59]([O:62][CH2:63][CH2:64][N:65]2[CH2:70][CH2:69][CH2:68][CH2:67]C2)[CH2:58][CH2:57]1>CN(C=O)C>[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:56]1[CH2:57][CH2:58][CH:59]([O:62][CH2:63][CH2:64][N:65]2[CH2:70][CH2:69][CH2:68][CH2:67]2)[CH2:60][CH2:61]1)=[O:5]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 248117402-Fluoro-5-[(4-oxo-3,4-dihydrophthalazin-1-yl)methyl]benzoic acidHCID 43167822HCID 43167822, compound

Product 1

HCID 577918434-(4-fluoro-3-(4-(2-(pyrrolidin-1-yl)ethoxy)piperidine-1-carbonyl)benzyl)phthalazin-1(2H)-oneYield 89.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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 DMF (4 mL), to this was added N-ethyl-N-isopropylpropan-2-amine (0.179 mL, 1.01 mmol) and then 4-(2-(pyrrolidin-1-yl)ethoxy)piperidine (109) (0.133 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 as a white solid (0.287 g, 89% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.65-1.81 (6H, m), 1.87-1.96 (3H, m), 2.53-2.61 (3H, m), 2.65-2.72 (2H, m), 3.04-3.14 (1H, m), 3.38-3.57 (3H, m), 3.61 (2H, t), 3.97-4.06 (1H, m), 4.28 (2H, s), 7.01 (1H, t), 7.21-7.33 (2H, m), 7.68-7.80 (3H, m), 8.43-8.48 (1H, m), 9.85-9.95 (1H, m); m/z (LC-MS, ESI+), RT=1.88 (M+H 479.5).

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-c3750c73ebff49ed8021b4b877299620
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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