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 2183990노트

반응식

HRID 2183990 반응식
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

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 10340Sodium Carbonate용매

반응 조건

온도
65 °C

실험 절차

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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-f004cc3071fb4df5b5fb8dabddf8ea0e
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06900215B2

반응 노트

불러오는 중…