Sodium Hydroxide → (2S)-N,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

HRID 1519704ノート

反応式

HRID 1519704 の反応式
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]#[C:10][C:11]2[CH:36]=[CH:35][C:14]([C:15]([N:17]([CH3:34])[C@:18]([CH3:33])([C:23]([NH:25][O:26][CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][O:28]3)=[O:24])[C:19]([NH:21][CH3:22])=[O:20])=[O:16])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1)=O.[CH2:37]1[CH2:43][O:42][CH2:41][CH2:40][NH:39][CH2:38]1.Cl.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(OCC)(=O)C.O.C(Cl)(Cl)Cl.C(O)(=O)C>[CH3:22][NH:21][C:19](=[O:20])[C@:18]([CH3:33])([N:17]([CH3:34])[C:15](=[O:16])[C:14]1[CH:35]=[CH:36][C:11]([C:10]#[C:9][C:6]2[CH:7]=[CH:8][C:3]([CH2:1][N:39]3[CH2:38][CH2:37][CH2:43][O:42][CH2:41][CH2:40]3)=[CH:4][CH:5]=2)=[CH:12][CH:13]=1)[C:23]([NH:25][O:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][O:28]1)=[O:24]

参加物

9

反応物 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 230902141,4-Oxazepane hydrochlorideHCID 86679270(2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

生成物 1

HCID 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収率 69.1%

試薬・触媒・溶媒 4

HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 6212Chloroform溶媒HCID 8857Ethyl Acetate溶媒

実験手順

TEA (1.6 mL) and acetic acid (0.8 mL) were added to a chloroform (13 mL) solution of (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (3.7 g) as obtained in Example 16-(1) and homomorpholine hydrochloride (1.6 g). Under ice cooling, sodium triacetoxyborohydride (2.6 g) was added in divided portions in a nitrogen atmosphere, and the mixture was stirred for 3.5 hours at room temperature. Water and ethyl acetate were added, the mixture was adjusted to pH 7.5 with a 1 mol/L sodium hydroxide aqueous solution, and then the organic layer was isolated. 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 chloroform/methanol=90/10) to obtain (2S)-N,2-dimethyl-2-[methyl(4-{[4-(1,4-oxazepan-4-ylmethyl)phenyl]ethynyl}benzoyl)amino]-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (light yellow solid) (3.0 g, 69%).

後処理

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

出典と根拠

ORDレコード
ord-47afd9a4eeb84e4686e00871f7cc2042
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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