Diisopropylethylamine → rac-N-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2,N-dimethyl-propionamide

HRID 220318ノート

反応式

HRID 220318 の反応式
[CH3:1][O:2][CH2:3][C:4]([CH2:9][O:10][CH3:11])([CH3:8])[C:5]([OH:7])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:45][N:46]([CH2:64][CH2:65][CH2:66][NH:67][CH3:68])[CH2:47][CH2:48][C:49]1([OH:63])[CH2:54][CH:53]2[CH2:55][CH2:56][CH:50]1[CH:51]=[C:52]2[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>C(Cl)Cl>[OH:63][C@@:49]1([CH2:48][CH2:47][N:46]([CH3:45])[CH2:64][CH2:65][CH2:66][N:67]([CH3:68])[C:5](=[O:7])[C:4]([CH2:3][O:2][CH3:1])([CH3:8])[CH2:9][O:10][CH3:11])[CH2:54][C@H:53]2[CH2:55][CH2:56][C@@H:50]1[CH:51]=[C:52]2[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 219119313-Methoxy-2-(methoxymethyl)-2-methylpropanoic acidHCID 68413377rac-(1R*,2R*,4R*)-2-{2-[methyl-(3-methylamino-propyl)-amino]-ethyl}-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol

生成物 1

HCID 68413389rac-N-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2,N-dimethyl-propionamide収率 90.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 65 mg 3-methoxy-2-methoxymethyl-2-methyl-propionic acid in 0.5 mL DCM was added 0.14 mL DIPEA followed by 133 mg HATU. The resulting mixture was stirred at rt for 20 min before 88 mg of rac-(1R*,2R*,4R*)-2-{2-[methyl-(3-methylamino-propyl)-amino]-ethyl}-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol, dissolved in 1 mL DCM was added. After stirring overnight the reaction was quenched with water. The water phase was extracted with DCM, the combined organic phases were washed with brine, dried and concentrated in vacuo. The residue was purified by CC with EtOAc-MeOH (3:1) to obtain 115 mg of rac-N-(3-{[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-methyl-amino}-propyl)-3-methoxy-2-methoxymethyl-2,N-dimethyl-propionamide as colorless oil.

後処理

  1. additionwas added
  2. customwas quenched with water
  3. extractionThe water phase was extracted with DCM
  4. washthe combined organic phases were washed with brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by CC with EtOAc-MeOH (3:1)

出典と根拠

ORDレコード
ord-93485bb4680b41159d26694fe08bc57a
出典データセット
uspto-grants-2012_06
特許番号
US08202885B2

反応ノート

読み込み中…