Diisopropylamine → 3-fluoro-N-(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide

HRID 1171271ノート

反応式

HRID 1171271 の反応式
[CH3:1][S:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:21](=[O:27])OC(C)(C)C)=[CH:12][CH:11]=2)[CH:6]=[CH:5][N:4]=1.[F:28][CH:29]1COCC(C2C(C(O)=O)=CC=CC=2)N1.[Cl-].ClC1N(C)[CH2:49][CH2:48][NH+]1C.[CH:53]([NH:56][CH:57]([CH3:59])[CH3:58])([CH3:55])C.[O:60]1[CH2:65][CH2:64]OCC1>Cl.C(Cl)Cl>[F:28][C:29]1[CH:48]=[C:49]([CH:58]=[C:57]([N:56]2[CH2:64][CH2:65][O:60][CH2:55][CH2:53]2)[CH:59]=1)[C:21]([NH:20][C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([O:9][C:7]2[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=2)=[CH:11][CH:12]=1)=[O:27]

参加物

8

反応物 5

HCID 7912DiisopropylamineHCID 312751,4-DioxaneHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 59553280t-Butyl(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)carbamateHCID 667380893-Fluoro-5-morpholinebenzoic acid

生成物 1

HCID 595530703-fluoro-N-(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of t-butyl (4-{[2-(methylthio) pyrimidin-4-yl]oxy}-1-naphthyl)carbamate (1.0 g, 2.61 mmol) in 4.0 M HCl in dioxane (10 ml) is stirred at room temperature for 1 h. The mixture is then evaporated to dryness. The residue is then dissolved in CH2Cl2 (5 ml) containing diisopropylamine (1.0 ml). To this mixture is added a solution of 3-fluoro-5-morpholinebenzoic acid (0.70 g, 3.13 mmol), 2-chloro-1,3-dimethylimidazolinium chloride (0.525 g, 3.13 mmol) and diisopropylamine (1.27 ml) in CH2Cl2 (10 ml) at room temperature. The mixture is stirred at room temperature overnight and then washed with saturated NaHCO3 solution, brine, dried over Na2SO4 and concentrated. The residue is purified by column chromatography on silica gel (10-60% EtOAc in hexane) to give 3-fluoro-N-(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide as an off-white solid (0.75 g). Mp: 189-190° C.; 1H NMR (300 MHz, CDCl3) δ 2.29 (s, 3H), 3.25 (t, J=4.8 Hz, 4H), 3.87 (t, J=5.1Hz, 4H), 6.53 (d, J=6.0 Hz, 1H), 6.75-6.80 (m, 1H), 7.07 (d, J=8.4 Hz, 1H), 7.30-7.33 (m, 2H), 7.49-7.56 (m, 2H), 7.89-7.97 (m, 3H), 8.16 (s, 1H), 8.36 (d, J=5.7 Hz, 1H); MS: 491 (M+1).

後処理

  1. customThe mixture is then evaporated to dryness
  2. dissolutionThe residue is then dissolved in CH2Cl2 (5 ml)
  3. additioncontaining diisopropylamine (1.0 ml)
  4. washwashed with saturated NaHCO3 solution, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue is purified by column chromatography on silica gel (10-60% EtOAc in hexane)

出典と根拠

ORDレコード
ord-320ab1a67d0446f8ace032408b521611
出典データセット
uspto-grants-2010_11
特許番号
US07829560B2

反応ノート

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