4-Methoxypiperidine → 5-chloro-4-(3-fluoro-5-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

HRID 1091811노트

반응식

HRID 1091811 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([CH2:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([F:22])[CH:21]=1)[C:16]([OH:18])=O)=[N:9][NH:8][C:7]2=[O:23].[CH3:24][O:25][CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10]([CH2:12][C:13]1[CH:14]=[C:15]([C:16]([N:29]3[CH2:30][CH2:31][CH:26]([O:25][CH3:24])[CH2:27][CH2:28]3)=[O:18])[CH:19]=[C:20]([F:22])[CH:21]=1)=[N:9][NH:8][C:7]2=[O:23]

참가 물질

5

반응물 3

HCID 776664-MethoxypiperidineHCID 81531DiisopropylethylamineHCID 577917753-((8-Chloro-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-5-fluorobenzoic acid

생성물 1

HCID 577918115-chloro-4-(3-fluoro-5-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

3-((8-chloro-4-oxo-3,4-dihydrophthalazin-1-yl)methyl)-5-fluorobenzoic acid (128), 4-methoxypiperidine and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate were dissolved in DMF (10 mL), to this was added DIPEA and the reaction was stirred for 1 hour. The solvent was evaporated to dryness and the gum was dissolved in acetonitrile (4 mL) 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 as a white foam (67.0 mg); 1H NMR (400.132 MHz, CDCl3) δ 1.89-1.40 (4H, m), 3.17-3.06 (1H, m), 3.34 (3H, s), 3.58-3.42 (3H, m), 4.00-3.84 (1H, m), 4.67 (2H, s), 6.97-6.89 (3H, m), 7.67 (1H, t), 7.81 (1H, d), 8.49 (1H, d), 10.29 (1H, s); m/z (LC-MS, ESI+), RT=1.93 (M+H 430).

후처리

  1. customThe solvent was evaporated to dryness
  2. dissolutionthe gum was dissolved in acetonitrile (4 mL)
  3. custompurified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 19 mm diameter, 100 mm length)
  4. additionFractions containing the desired compound
  5. customwere evaporated to dryness

출처 및 근거

ORD 기록
ord-4c4183d11af946f4ac9d31df261bca5a
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129380B2

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