Sulfuric Acid → (2S)-N-hydroxy-N',2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]propanediamide

HRID 1519705ノート

反応式

HRID 1519705 の反応式
S(=O)(=O)(O)O.[CH3:6][NH:7][C:8](=[O:47])[C@:9]([CH3:46])([N:20]([CH3:45])[C:21](=[O:44])[C:22]1[CH:27]=[CH:26][C:25]([C:28]#[C:29][C:30]2[CH:35]=[CH:34][C:33]([CH2:36][N:37]3[CH2:43][CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[CH:32][CH:31]=2)=[CH:24][CH:23]=1)[C:10]([NH:12][O:13]C1CCCCO1)=[O:11].[OH-].[Na+].C(=O)([O-])O.[Na+].[Cl-].[Na+]>C(OCC)(=O)C.O.O1CCOCC1>[OH:13][NH:12][C:10](=[O:11])[C@@:9]([CH3:46])([N:20]([CH3:45])[C:21](=[O:44])[C:22]1[CH:23]=[CH:24][C:25]([C:28]#[C:29][C:30]2[CH:35]=[CH:34][C:33]([CH2:36][N:37]3[CH2:43][CH2:42][CH2:41][O:40][CH2:39][CH2:38]3)=[CH:32][CH:31]=2)=[CH:26][CH:27]=1)[C:8]([NH:7][CH3:6])=[O:47]

参加物

9

反応物 5

HCID 1118Sulfuric AcidHCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 86679271(2S)-N,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

生成物 1

HCID 71598567(2S)-N-hydroxy-N',2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]propanediamide収率 66.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒2 回HCID 312751,4-Dioxane溶媒

実験手順

A 1 mol/L sulfuric acid aqueous solution (16 mL) was added dropwise, under water cooling, to a 1,4-dioxane (6.0 mL) suspension of (2S)-N,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (3.0 g) as obtained in Example 16-(2), and the mixture was stirred for 2 hours and 50 minutes at room temperature. Water and ethyl acetate were added, and the aqueous layer was isolated. The isolate was adjusted to pH 7 with 20% sodium hydroxide and a saturated aqueous solution of sodium hydrogen carbonate, and then ethyl acetate and sodium chloride were added, followed by isolating the organic layer. The extract was washed with brine, and dried over anhydrous sodium sulfate. Then, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=100/0→60/40, followed by gradient elution with chloroform/methanol=98/2→90/10) to obtain (2S)-N-hydroxy-N′,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]propanediamide (Compound 376, pale yellow solid) (1.7 g, 65%).

後処理

  1. customthe aqueous layer was isolated
  2. customby isolating the organic layer
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThen, the desiccant was filtered out
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=100/0→60/40, followed by gradient elution with chloroform/methanol=98/2→90/10)

出典と根拠

ORDレコード
ord-0bd826279f764bc3a9d947e6c8d75a70
出典データセット
uspto-grants-2015_07
特許番号
US09073821B2

反応ノート

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