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

HRID 1091811ノート

反応式

HRID 1091811 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-4c4183d11af946f4ac9d31df261bca5a
出典データセット
uspto-grants-2012_03
特許番号
US08129380B2

反応ノート

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