Sodium Carbonate → 3-(1H-indol-5-yl)-5-(3-methoxy-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

HRID 333148ノート

反応式

HRID 333148 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[NH:16][CH:15]=[CH:14]4)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[CH3:30][O:31][C:32]1[CH:46]=[C:45](B2OC(C)(C)C(C)(C)O2)[CH:44]=[CH:43][C:33]=1[O:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>CC#N.CO.CC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[NH:16]1[C:17]2[C:13](=[CH:12][C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([C:45]5[CH:44]=[CH:43][C:33]([O:34][CH2:35][CH2:36][N:37]6[CH2:38][CH2:39][NH:40][CH2:41][CH2:42]6)=[C:32]([O:31][CH3:30])[CH:46]=5)[CH:3]=4)[NH:8][CH:9]=3)=[CH:19][CH:18]=2)[CH:14]=[CH:15]1

参加物

9

反応物 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 667791765-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine2 回HCID 667799091-(2-(2-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)piperazine

生成物 1

HCID 462345053-(1H-indol-5-yl)-5-(3-methoxy-4-(2-(piperazin-1-yl)ethoxy)phenyl)-1H-pyrrolo[2,3-b]pyridine

試薬・触媒・溶媒 4

HCID 6102075Dichlorobis(triphenylphosphine)palladium触媒HCID 180Acetone溶媒HCID 887Methanol溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
150 °C

実験手順

To a solution of 5-bromo-3-(1H-indol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (Intermediate B) (92 mg, 0.20 mmol) in CH3CN (2 mL) in a Personal Chemistry microwave reaction vial was added 1-(2-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)piperazine (Intermediate AM) (72 mg, 0.20 mmol), bis(triphenylphosphine)-palladium(II)dichloride (20 mg, 0.028 mmol), and 1 M Na2CO3 (2 mL). The resulting mixture was de-gassed with Ar for 10 min, after which it was heated at 150° C. for 25 min in a Personal Chemistry Optimizer. The organic layer was separated, filtered, and concentrated in vacuo to give Intermediate AN. The residue was dissolved in MeOH (3 mL) and acetone (2 mL), and 2 M NaOH (1.5 mL) was added. The resulting mixture was stirred at 50° C. for 2 h, after which it was partitioned between EtOAc and 1 M NaOH. The organic layer was separated, dried over MgSO4, filtered, and stripped to give a residue that was subjected to preparatory HPLC to yield the title compound. HPLC retention time: 1.29 minutes; MS ESI (m/z) 468.6 (M+1)+, calc. 467.

後処理

  1. customThe resulting mixture was de-gassed with Ar for 10 min
  2. customThe organic layer was separated
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give Intermediate AN
  6. customafter which it was partitioned between EtOAc and 1 M NaOH
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customto give a residue that

出典と根拠

ORDレコード
ord-683109598cdb43cea04b7c19d113445a
出典データセット
uspto-grants-2014_11
特許番号
US08877772B2

反応ノート

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