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

HRID 1091796
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HRID 1091796 반응식
[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][CH2:66]2)[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: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][CH2:66]2)[CH2:58][CH2:57]1)=[O:5]
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참가 물질

6

반응물 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 431678221-[2-(Piperidin-4-yloxy)ethyl]piperidine

생성물 1

HCID 577917974-(4-fluoro-3-(4-(2-(piperidin-1-yl)ethoxy)piperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one
수율 20.9%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

실험 절차

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-(2-(piperidin-4-yloxy)ethyl)piperidine (115) (0.214 g, 1.01 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 compound (0.069 g, 20.74% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.36-1.45 (2H, m), 1.64-1.94 (8H, m), 2.37-2.50 (4H, m), 2.55 (2H, t), 3.03-3.15 (1H, m), 3.37-3.49 (1H, m), 3.50-3.65 (4H, m), 3.92-4.04 (1H, m), 4.30 (2H, s), 7.00 (1H, t), 7.21-7.32 (2H, m), 7.68-7.79 (3H, m), 8.43-8.49 (1H, m), 10.49 (1H, s); m/z (LC-MS, ESI+), RT=2.01 (M+H 493.5).

후처리

  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

출처 및 근거

ORD 기록
ord-1d4f1a55fa364fd5b356d94e17e60b8f
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08129380B2

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