4-Methylmorpholine → rac-8-[(2,6-Difluorobenzyl)oxy]-N-[1-(3,4-difluorophenyl)-2-hydroxyethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 1624126ノート

反応式

HRID 1624126 の反応式
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16](O)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.F[B-](F)(F)F.N1(O[C+](N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:53][CH:54]([C:57]1[CH:62]=[CH:61][C:60]([F:63])=[C:59]([F:64])[CH:58]=1)[CH2:55][OH:56]>ClCCl>[F:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:2]([F:1])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:53][CH:54]([C:57]3[CH:62]=[CH:61][C:60]([F:63])=[C:59]([F:64])[CH:58]=3)[CH2:55][OH:56])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 220488782-Amino-2-(3,4-difluorophenyl)ethanolHCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 178484679HCID 178484679、化合物

生成物 1

HCID 90115443rac-8-[(2,6-Difluorobenzyl)oxy]-N-[1-(3,4-difluorophenyl)-2-hydroxyethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide収率 3.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

100 mg (0.31 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 111 mg (0.35 mmol) of (benzotriazol-1-yloxy)bisdimethylaminomethylium fluoroborate (TBTU) and 159 mg (1.57 mmol) of 4-methylmorpholine were initially charged in 2.0 ml of dichloromethane. After 10 min at RT, 142 mg (0.35 mmol) of 2-amino-2-(3,4-difluorophenyl)-ethanol were added and the mixture was stirred at room temperature overnight. The reaction solution was concentrated, and acetonitrile/methanol/water was added. A solid precipitated out, and this solid was filtered off and purified by chromatography on silica gel (mobile phase: dichloromethane:THF=10:1→5:1). The combined product fractions were concentrated and then triturated with acetonitrile, and the solid was filtered off and washed with methanol. This gave 39 mg of the target compound (26% of theory, purity 95%). After some time, the filtrate produced more solid; this gave another 5 mg of the target compound (3.3% of theory, purity 99%).

後処理

  1. concentrationThe reaction solution was concentrated
  2. additionacetonitrile/methanol/water was added
  3. customA solid precipitated out
  4. filtrationthis solid was filtered off
  5. custompurified by chromatography on silica gel (mobile phase: dichloromethane:THF=10:1→5:1)
  6. concentrationThe combined product fractions were concentrated
  7. customtriturated with acetonitrile
  8. filtrationthe solid was filtered off
  9. washwashed with methanol
  10. customAfter some time, the filtrate produced more solid

出典と根拠

ORDレコード
ord-7d7cc4b414d942d6b6e5bb4bb67e5e4d
出典データセット
uspto-grants-2014_07
特許番号
US08778964B2

反応ノート

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