Sodium Carbonate → N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(4-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide

HRID 2241276ノート

反応式

HRID 2241276 の反応式
[CH3:1][O:2][C:3]1[CH:37]=[CH:36][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]([CH:27]5[CH2:31][CH2:30][N:29]([CH3:32])[C:28]5=[O:33])=[O:26])=[CH:20][C:19]=4[F:34])=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[CH3:38][NH:39][C:40]([C:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1)=[O:41].C([O-])([O-])=O.[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COCCOC>[F:34][C:19]1[CH:20]=[C:21]([NH:24][C:25]([CH:27]2[CH2:31][CH2:30][N:29]([CH3:32])[C:28]2=[O:33])=[O:26])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][C:6]3[CH:36]=[CH:37][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:9]=[C:10]([C:45]3[CH:46]=[CH:47][C:42]([C:40](=[O:41])[NH:39][CH3:38])=[CH:43][CH:44]=3)[C:11]=12

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 27735264-(Methylcarbamoyl)benzeneboronic acidHCID 68516437N-(3-fluoro-4-(3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide

生成物 1

HCID 68514554N-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(4-(methylcarbamoyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide収率 53.4%

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
60 °C

実験手順

A 50 mL round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-methyl-2-oxopyrrolidine-3-carboxamide (20.0 mg, 0.0325 mmol), 4-(methylcarbamoyl)phenylboronic acid (17.5 mg, 0.0975 mmol), tetrakis(triphenylphosphine) palladium (7.51 mg, 0.00650 mmol), Na2CO3 (0.0812 ml, 0.162 mmol) and DME (10 mL). The reaction mixture was stirred at 60° C. for 4 hours, and then partitioned between EtOAc and H2O. The phases were separated, and the aqueous phase was re-extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude product. The crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (10.8 mg, 53.4%). LRMS (APCI pos) m/e 623 (M+1).

後処理

  1. custompartitioned between EtOAc and H2O
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a crude product
  8. customThe crude product was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 100/1 to 10/1

出典と根拠

ORDレコード
ord-8e145ad24e5447e9a9585d1d6f209644
出典データセット
uspto-grants-2010_05
特許番号
US07723330B2

反応ノート

読み込み中…