Cesium carbonate → (5-(3-Amino-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol

HRID 1662201ノート

反応式

HRID 1662201 の反応式
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[F:11])[C:4]([C:19]2[CH:20]=[C:21]([CH3:29])[C:22]([O:27][CH3:28])=[C:23]([CH2:25][OH:26])[CH:24]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14](Br)[CH:13]=2)[N:3]=1.[N:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.CCO.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[F:11])[C:4]([C:19]2[CH:20]=[C:21]([CH3:29])[C:22]([O:27][CH3:28])=[C:23]([CH2:25][OH:26])[CH:24]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:34]3[CH:35]=[N:30][CH:31]=[N:32][CH:33]=3)[CH:13]=2)[N:3]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 58579488(5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol

生成物 1

HCID 58579497(5-(3-Amino-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol収率 74.3%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 86587095Dimethoxyethane ethanol water溶媒

実験手順

(5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol (338 mg, 0.74 mmol), pyrimidine-5-boronic acid (110 mg, 0.89 mmol), cesium carbonate (726 mg, 2.23 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (60.6 mg, 0.07 mmol) were dissolved in DME:EtOH:water (6:3:1) (5 mL) and irradiated in a microwave oven for 20 min at 150° C. The solvent was evaporated in vacuo and to the residue was added water, 2 M HCl solution to reach pH˜7, and EtOAc. The organic phase was collected, dried and filtered. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to give 250 mg (74%) of the title compound.

後処理

  1. customirradiated in a microwave oven for 20 min at 150° C
  2. customThe solvent was evaporated in vacuo and to the residue
  3. additionwas added water, 2 M HCl solution
  4. customThe organic phase was collected
  5. customdried
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-0d854741bca347e5980e91958ca2c20d
出典データセット
uspto-grants-2011_10
特許番号
US08030500B2

反応ノート

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