Sodium Bicarbonate → HCID 86679273、化合物

HRID 1519707ノート

反応式

HRID 1519707 の反応式
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:15]([C:17]1[CH:22]=[CH:21][C:20]([C:23]#[C:24][C:25]2[CH:50]=[CH:49][C:28]([C:29]([N:31]([CH3:48])[C@:32]([CH3:47])([C:37]([NH:39][O:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][O:42]3)=[O:38])[C:33]([NH:35][CH3:36])=[O:34])=[O:30])=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)=O.Cl.[F:52][CH2:53][CH2:54][O:55][CH:56]1[CH2:59][NH:58][CH2:57]1.C(=O)([O-])O.[Na+]>CN1C(=O)CCC1.C(OCC)(=O)C.O>[F:52][CH2:53][CH2:54][O:55][CH:56]1[CH2:59][N:58]([CH2:15][C:17]2[CH:18]=[CH:19][C:20]([C:23]#[C:24][C:25]3[CH:26]=[CH:27][C:28]([C:29]([N:31]([CH3:48])[C@:32]([CH3:47])([C:37]([NH:39][O:40][CH:41]4[CH2:46][CH2:45][CH2:44][CH2:43][O:42]4)=[O:38])[C:33]([NH:35][CH3:36])=[O:34])=[O:30])=[CH:49][CH:50]=3)=[CH:21][CH:22]=2)[CH2:57]1

参加物

8

反応物 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 768479003-(2-Fluoroethoxy)azetidine 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 86679273HCID 86679273、化合物収率 81%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

Sodium triacetoxyborohydride (0.10 g) was added to a solution in NMP (1.5 mL) of (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (0.15 g) as obtained in Example 16-(1) and 3-(2-fluoroethoxy)azetidine hydrochloride (63 mg) as obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere. The mixture was stirred for 40 minutes at room temperature. Water and ethyl acetate were added, and the mixture was adjusted to pH 7.5 with a saturated aqueous solution of sodium hydrogen carbonate, whereafter 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=80/20→50/50) to obtain (2S)-2-[{4-[(4-{[3-(2-fluoroethoxy)azetidin-1-yl]methyl}phenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow oil) (0.14 g, 81%).

後処理

  1. customas obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere
  2. customwas isolated
  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=80/20→50/50)

出典と根拠

ORDレコード
ord-177d3f4d07e44c329c5dc317a601b186
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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