Sodium Carbonate → (1S,2R)-4'-(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)-4-(2-morpholin-4-yl-ethoxy)biphenyl-3-carbonitrile

HRID 380006

反応式

HRID 380006 の反応式
[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8](B(O)O)=[CH:7][CH:6]=1.BrC1C=CC(N[CH2:33][CH2:34][N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)=C(C=1)C#N.[C:41](=[O:44])([O-])[O-].[Na+].[Na+]>C(O)C.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>[OH:1][C@H:2]([CH2:15][CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1)[C@H:3]([CH3:14])[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:15]2[CH:2]=[CH:3][C:41]([O:44][CH2:33][CH2:34][N:35]3[CH2:36][CH2:37][O:38][CH2:39][CH2:40]3)=[C:17]([C:18]#[N:19])[CH:16]=2)=[CH:7][CH:6]=1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 183676075-Bromo-2-(2-morpholinoethylamino)benzonitrileHCID 54413593(1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid

生成物 1

HCID 70244930(1S,2R)-4'-(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)-4-(2-morpholin-4-yl-ethoxy)biphenyl-3-carbonitrile

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒

反応条件

温度
90 °C

実験手順

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.190 g, Example 33), 5-bromo-2-(2-morpholin-4-yl-ethylamino)benzonitrile (0.31 g, Example 47a)), 2M aqueous sodium carbonate (0.75 ml) and tetrakis(triphenylphosphine)palladium (0) (0.025 g) in ethanol (2 ml). The reaction mixture was heated at 90° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure, taken up in ethanol and concentrated again (twice). The residue was triturated with acetone and then filtered through silica gel. The filtrate was concentrated under reduced pressure, dissolved in dichloromethane, filtered and purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane to give an oil which crystallised under high vacuum over 24 hours. Trituration with diethyl ether resulted in isolation of the title compound as a foam (0.19 g).

後処理

  1. customPrepared
  2. temperatureAfter cooling
  3. concentrationthe solution was concentrated under reduced pressure
  4. concentrationconcentrated again (twice)
  5. customThe residue was triturated with acetone
  6. filtrationfiltered through silica gel
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. dissolutiondissolved in dichloromethane
  9. filtrationfiltered
  10. custompurified by normal-phase HPLC
  11. washeluting with a gradient of 0-25% ethanol in dichloromethane
  12. customto give an oil which
  13. customcrystallised under high vacuum over 24 hours

出典と根拠

ORDレコード
ord-9a64ade7a93c44f48d15012925f4759c
出典データセット
uspto-grants-2001_10
特許番号
US06300352B1

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