Bis(2-oxo-3-oxazolidinyl)phosphinic chloride → 1h-Pyrrolo[3,2-b]pyridine-2-carboxamide,1-[[5-(5-chloro-2-thienyl)-3-isoxazolyl]methyl]-n-[1-(1-methylethyl)-4-piperidinyl]-

HRID 2250433

反応式

HRID 2250433 の反応式
[Cl:1][C:2]1[S:6][C:5]([C:7]2[O:11][N:10]=[C:9]([CH2:12][N:13]3[C:21]4[C:16](=[N:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=[C:14]3[C:22](O)=[O:23])[CH:8]=2)=[CH:4][CH:3]=1.Cl.[CH:26]([N:29]1[CH2:34][CH2:33][CH:32]([NH2:35])[CH2:31][CH2:30]1)([CH3:28])[CH3:27].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1>ClCCl.C(N(CC)CC)C>[CH:26]([N:29]1[CH2:34][CH2:33][CH:32]([NH:35][C:22]([C:14]2[N:13]([CH2:12][C:9]3[CH:8]=[C:7]([C:5]4[S:6][C:2]([Cl:1])=[CH:3][CH:4]=4)[O:11][N:10]=3)[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)=[O:23])[CH2:31][CH2:30]1)([CH3:28])[CH3:27]

参加物

6

反応物 3

HCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 230334601-Isopropylpiperidin-4-amine hydrochlorideHCID 692269921h-Pyrrolo[3,2-b]pyridine-2-carboxylic acid,1-[[5-(5-chloro-2-thienyl)-3-isoxazolyl]methyl]-

生成物 1

HCID 99131941h-Pyrrolo[3,2-b]pyridine-2-carboxamide,1-[[5-(5-chloro-2-thienyl)-3-isoxazolyl]methyl]-n-[1-(1-methylethyl)-4-piperidinyl]-

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

To a suspension of 50 mg 1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid, 36 mg 1-isopropyl-piperidin-4-ylamine hydrochloride and 35 mg bis(2-oxo-3-oxazolidinyl)phosphinic chloride in 1 mL dichloromethane, 77 μl triethylamine were added at room temperature and the mixture was stirred for 16 hours. After removing of the solvent under reduced pressure, the residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid). The fractions containing the product were evaporated and lyophilized to yield a white residue which was partitioned between 5 mL aqueous 0.1 N sodium hydroxide solution and 5 mL ethyl acetate. The organic layer was washed with additional water and then dried over sodium sulphate. After filtration and removal of the solvent under reduced pressure, a white solid was obtained.

後処理

  1. additionwere added at room temperature
  2. customAfter removing of the solvent under reduced pressure
  3. customthe residue was purified by preparative HPLC (
  4. washC18 reverse phase column, elution with a water/acetonitrile gradient with 0.1% trifluoroacetic acid)
  5. additionThe fractions containing the product
  6. customwere evaporated
  7. customto yield a white residue which
  8. customwas partitioned between 5 mL aqueous 0.1 N sodium hydroxide solution and 5 mL ethyl acetate
  9. washThe organic layer was washed with additional water
  10. dry with materialdried over sodium sulphate
  11. filtrationAfter filtration and removal of the solvent under reduced pressure
  12. customa white solid was obtained

出典と根拠

ORDレコード
ord-f954f163e0ed4341b8c473ef5f16f735
出典データセット
uspto-grants-2008_01
特許番号
US07317027B2

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