4-Methylmorpholine → HCID 21088992、化合物

HRID 350906ノート

反応式

HRID 350906 の反応式
[Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[CH3:18])[C:12]([OH:14])=O)[C:5]([CH3:19])=[N:4][C:3]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[F:29].[CH2:30]([O:34]C(Cl)=O)C(C)C.C[N:39]1CC[O:42][CH2:41][CH2:40]1>CN(C)C=O.ClCCl>[Br:1][C:2]1[C:7](=[O:8])[N:6]([C:9]2[CH:10]=[C:11]([CH:15]=[CH:16][C:17]=2[CH3:18])[C:12]([NH:39][CH2:40][C@H:41]([OH:42])[CH2:30][OH:34])=[O:14])[C:5]([CH3:19])=[N:4][C:3]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=1[F:29]

参加物

6

反応物 3

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 210892453-[5-Bromo-4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid

生成物 1

HCID 21088992HCID 21088992、化合物収率 43%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of 3-[5-bromo-4-[(2,4-difluorobenzyl)oxy]-2-methyl-6-oxopyrimidin-1(6H)-yl]-4-methylbenzoic acid (0.3 g, 0.65 mmol) in dimethylformamide (3.0 mL) at −10° C. was added isobutylchloroformate (0.13 g, 0.92 mmol) followed by the addition of N-methylmorpholine (0.130 g, 1.28 mmol). The mixture was stirred for 10 min. under argon atmosphere. The reaction mixture was then stirred at room temperature for 30 min, cooled to 0° C., and added S-3-amino-1,2 propanediol (0.118 g, 1.3 mmol). The resulting mixture was stirred at room temperature for 1.5 h, concentrated in vacuo, and the residue was purified by reverse-phase HPLC using 10–90% CH3CN/Water gradient (40 min) at a flow rate of 80 mL/min. The appropriate fractions (MH+, m/z=538) were combined, and freeze-dried to give a white solid. This was dissolved in dichloromethane (20 mL), washed successively with 5% sodium bicarbonate (2×15 mL), water (2×20 mL), dried (Na2SO4), and concentrated to dryness to afford the racemic title compound (0.15 g, 43%) as a white amorphous substance: 1H NMR (CD3OD/400 MHz) δ 7.89 (dd 1H, J=1.6 Hz, 8.0 Hz), 7.66 (d, 1H, J=1.6 Hz), 7.60 (m, 1H), 7.52 (d, 1H, J=8.0 Hz), 7.01 (m, 2H), 5.54 (abq, 2H), 3.77 (m, 1H), 3.51 (m,3H), 3.38 (m, 1H), 2.74 (s, 3H), and 2.11(s, 3H); ES-HRMS m/z 538.0782 (M+H calcd for C23H23N3O5F2Br requires 538.0784). 19F NMR(CD3OD/400 MHz) −111.85(m) and −115.91 (m).

後処理

  1. stirringThe reaction mixture was then stirred at room temperature for 30 min
  2. stirringThe resulting mixture was stirred at room temperature for 1.5 h
  3. concentrationconcentrated in vacuo
  4. customthe residue was purified by reverse-phase
  5. custom10–90% CH3CN/Water gradient (40 min)
  6. customfreeze-dried
  7. customto give a white solid
  8. washwashed successively with 5% sodium bicarbonate (2×15 mL), water (2×20 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-403c374370c64f4292398ad9842ae69c
出典データセット
uspto-grants-2007_02
特許番号
US07183287B2

反応ノート

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