2-(3-Bromoimidazo[1,2-a]pyrimidin-7-yl)propan-2-ol → 2-[3-(2,4-Difluoro-3-(pyridin-3-yl)phenyl)imidazo[1,2-alpha]pyrimidin-7-yl]propan-2-ol

HRID 2183990ノート

反応式

HRID 2183990 の反応式
Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:10][C:5]2=[N:4][CH:3]=1.[F:15][C:16]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[C:20]([F:28])[CH:19]=[CH:18][C:17]=1B(O)O>O1CCCC1.C(=O)([O-])[O-].[Na+].[Na+].O.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>[F:28][C:20]1[C:21]([C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)=[C:16]([F:15])[CH:17]=[CH:18][C:19]=1[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:14])([CH3:13])[CH3:12])=[N:10][C:5]2=[N:4][CH:3]=1

参加物

7

反応物 2

HCID 112422822-(3-Bromoimidazo[1,2-a]pyrimidin-7-yl)propan-2-olHCID 222400962,4-Difluoro-3-(pyridin-3-yl)benzeneboronic acid

生成物 1

HCID 99691392-[3-(2,4-Difluoro-3-(pyridin-3-yl)phenyl)imidazo[1,2-alpha]pyrimidin-7-yl]propan-2-ol

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 10340Sodium Carbonate溶媒

反応条件

温度
65 °C

実験手順

A mixture of 2-(3-bromoimidazo[1,2-α]pyrimidin-7-yl)propan-2-ol (256 mg, 1.0 mmol) and 2,4-difluoro-3-(pyridin-3-yl)benzeneboronic acid (352 mg, 1.5 mmol) in tetrahydrofuran (3 ml) and sodium carbonate (1.25 ml of a 2M solution in water, 2.5 mmol) was degassed with nitrogen for 10 min. Tetrakis(triphenylphosphine)palladium(0) (58 mg, 0.05 mmol) was added and this mixture was heated at 65° C. for 24 h. The reaction was cooled to ambient temperature then partitioned between dichloromethane and saturated aqueous sodium hydrogencarbonate. The organics were dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica gel eluting with dichloromethane (containing 1% conc. ammonia) on a gradient of methanol (1-5%) gave 2-[3-(2,4-difluoro-3-(pyridin-3-yl)phenyl)imidazo[1,2-α]pyrimidin-7-yl]propan-2-ol as a pale yellow oil which solidified on standing (200 mg, 44%). Bis-hydrochloride salt (from ethyl acetate/ethanol): δH (360 MHz, d6-DMSO) 1.56 (6H, s), 7.62 (1H, t, J 9), 7.79-7.84 (1H, m), 7.86 (1H, s), 7.88 (1H, s), 8.32 (1H, d, J 8), 8.54 (1H, s), 8.80 (1H, d, J 5), 8.98 (1H, s), 9.27 (1H, dd, J 7 and 3).

後処理

  1. customwas degassed with nitrogen for 10 min
  2. temperatureThe reaction was cooled to ambient temperature
  3. customthen partitioned between dichloromethane and saturated aqueous sodium hydrogencarbonate
  4. dry with materialThe organics were dried over anhydrous magnesium sulfate
  5. filtrationfiltered and pre-adsorbed onto silica
  6. customPurification by chromatography on silica gel eluting with dichloromethane (containing 1% conc. ammonia) on a gradient of methanol (1-5%)

出典と根拠

ORDレコード
ord-f004cc3071fb4df5b5fb8dabddf8ea0e
出典データセット
uspto-grants-2005_05
特許番号
US06900215B2

反応ノート

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