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

HRID 1171271노트

반응식

HRID 1171271 반응식
[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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 313Hydrochloric Acid용매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-320ab1a67d0446f8ace032408b521611
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07829560B2

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