Sodium Carbonate → 2-{3-[2-(3,4-Difluorophenyl)pyrimidin-4-yl]-8-fluoroimidazo[1,2-alpha]pyridin-7-yl}propan-2-ol

HRID 1765103ノート

反応式

HRID 1765103 の反応式
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].Cl[C:13]1[N:18]=[C:17]([C:19]2[N:23]3[CH:24]=[CH:25][C:26]([C:29]([O:32][Si](CC)(CC)CC)([CH3:31])[CH3:30])=[C:27]([F:28])[C:22]3=[N:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:13]2[N:18]=[C:17]([C:19]3[N:23]4[CH:24]=[CH:25][C:26]([C:29]([OH:32])([CH3:30])[CH3:31])=[C:27]([F:28])[C:22]4=[N:21][CH:20]=3)[CH:16]=[CH:15][N:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 878862453-(2-Chloropyrimidin-4-yl)-8-fluoro-7-[2-(triethylsilyloxy)prop-2-yl]imidazo[1,2-alpha]pyridine

生成物 1

HCID 100000682-{3-[2-(3,4-Difluorophenyl)pyrimidin-4-yl]-8-fluoroimidazo[1,2-alpha]pyridin-7-yl}propan-2-ol

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒

実験手順

3,4-Difluorophenylboronic acid (90 mg, 0.57 mmol), 3-(2-chloropyrimidin-4-yl)-8-fluoro-7-[2-(triethylsilyloxy)prop-2-yl]imidazo[1,2-α]pyridine (120 mg, 0.29 mmol), tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.015 mmol), THF (1.4 ml) and aqueous Na2CO3 solution (2M; 0.44 ml) were combined and heated to reflux for 18 h. On cooling, the mixture was partitioned between 2M NaOH solution (2 ml) and CH2Cl2 (3 ml) and the phases separated using a phase-separation cartridge. The organic fraction was purified by column chromatography (silica, 90% EtOAc/isohexane), then the silyl protection removed by treatment with an ethanolic solution of 37% hydrochloric acid (5 drops in 2 ml of ethanol). After 48 h, the solution was concentrated in vacuo and the residue partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over MgSO4, filtered, concentrated and the residue purified by column chromatography (silica, EtOAc) affording the title compound as a white amorphous solid (158 mg): δH (360 MHz, CDCl3) 1.76 (6H, s), 7.00-7.20 (2H, m), 7.40-7.70 (2H, m), 8.20-8.40 (1H, m), 8.36 (1H, s), 8.80 (1H, m), 9.90-9.92 (1H, m); m/z (ES+) 385 (100%, [MH]+).

後処理

  1. temperatureheated
  2. temperatureto reflux for 18 h
  3. temperatureOn cooling
  4. customthe mixture was partitioned between 2M NaOH solution (2 ml) and CH2Cl2 (3 ml)
  5. customthe phases separated
  6. customThe organic fraction was purified by column chromatography (silica, 90% EtOAc/isohexane)
  7. customthe silyl protection removed by treatment with an ethanolic solution of 37% hydrochloric acid (5 drops in 2 ml of ethanol)
  8. concentrationthe solution was concentrated in vacuo
  9. customthe residue partitioned between EtOAc and saturated aqueous NaHCO3
  10. dry with materialThe organic phase was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customthe residue purified by column chromatography (silica, EtOAc)

出典と根拠

ORDレコード
ord-e66fd568fd124f9a987b28261c7c5820
出典データセット
uspto-grants-2007_06
特許番号
US07226926B2

反応ノート

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