Dichloromethane → 7-(3-Fluoro-4-(2-hydroxyethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 335268

反応式

HRID 335268 の反応式
Br[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:19]=[C:18]([C:20](=[O:36])[NH:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[N:29]4[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]4)[CH:17]=[CH:16][C:15]=3[F:37])=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[F:38][C:39]1[CH:40]=[C:41](B(O)O)[CH:42]=[CH:43][C:44]=1[C:45](=[O:50])[NH:46][CH2:47][CH2:48][OH:49].C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>CN(C=O)C.CCOC(C)=O.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]>[F:38][C:39]1[CH:40]=[C:41]([C:2]2[CH:7]=[CH:6][N:5]3[C:8]([C:11]([NH:13][C:14]4[CH:19]=[C:18]([C:20](=[O:36])[NH:21][CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[N:29]5[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]5)[CH:17]=[CH:16][C:15]=4[F:37])=[O:12])=[CH:9][N:10]=[C:4]3[CH:3]=2)[CH:42]=[CH:43][C:44]=1[C:45](=[O:50])[NH:46][CH2:47][CH2:48][OH:49]

参加物

9

反応物 4

HCID 6344Dichloromethane2 回HCID 10796Cesium carbonate2 回HCID 44717645(3-Fluoro-4-((2-hydroxyethyl)carbamoyl)phenyl)boronic acid2 回HCID 712830957-Bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

生成物 1

HCID 712834897-(3-Fluoro-4-(2-hydroxyethylcarbamoyl)phenyl)-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide

試薬・触媒・溶媒 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A mixture comprising 7-bromo-N-(2-fluoro-5-(2-(4-methylpiperazin-1-yl)benzylcarbamoyl)phenyl)imidazo[1,2-a]pyridine-3-carboxamide (Ex 1.1, step 1) (120 mg, 0.212 mmol), 3-fluoro-4-(2-hydroxyethylcarbamoyl)phenylboronic acid (48.2 mg, 0.212 mmol), cesium carbonate (69.1 mg, 0.212 mmol) and PdCl2(dppf).CH2Cl2 adduct (17.33 mg, 0.021 mmol) in DMF (3 ml) under N2 was heated at 85° C. for 2 hrs. Further portions of 3-fluoro-4-(2-hydroxyethylcarbamoyl)phenylboronic acid (48.2 mg, 0.212 mmol), cesium carbonate (69.1 mg, 0.212 mmol) and PdCl2(dppf).CH2Cl2 adduct (17.33 mg, 0.021 mmol) were added and heating continued at 100° C. overnight. The reaction mixture was diluted with EtOAc and water and the biphasic mixture was filtered. The filtercake was washed with MeOH and the filtrate was concentrated under vacuum. Purification of the crude residue by chromatography on silica eluting with 0-20% NH3MeOH/DCM afforded a beige solid. The solid was triturated with THF/ether and dried in vacuo at 45° C. overnight to afford the title compound;

後処理

  1. temperatureheating
  2. filtrationthe biphasic mixture was filtered
  3. washThe filtercake was washed with MeOH
  4. concentrationthe filtrate was concentrated under vacuum
  5. customPurification of the crude residue by chromatography on silica eluting with 0-20% NH3MeOH/DCM
  6. customafforded a beige solid
  7. customThe solid was triturated with THF/ether
  8. customdried in vacuo at 45° C. overnight

出典と根拠

ORDレコード
ord-13c1f3bd6e6b47b9aca5b42eaaf0ed89
出典データセット
uspto-grants-2014_11
特許番号
US08883819B2

関連ノート

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