Diisopropylethylamine → 1-[butyl(methyl)amino]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isoquinoline-7-carboxamide

HRID 14264

反応式

HRID 14264 の反応式
[CH2:1]([N:5]([CH3:19])[C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([OH:18])=O)[CH:14]=2)[CH:9]=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:53][C@@H:54]([CH2:68][C:69]1[CH:74]=[C:73]([F:75])[CH:72]=[C:71]([F:76])[CH:70]=1)[C@H:55]([OH:67])[CH2:56][NH:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[C:61]([CH2:65][CH3:66])[CH:60]=1>C(Cl)Cl>[CH2:1]([N:5]([CH3:19])[C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([NH:53][C@@H:54]([CH2:68][C:69]3[CH:70]=[C:71]([F:76])[CH:72]=[C:73]([F:75])[CH:74]=3)[C@H:55]([OH:67])[CH2:56][NH:57][CH2:58][C:59]3[CH:64]=[CH:63][CH:62]=[C:61]([CH2:65][CH3:66])[CH:60]=3)=[O:18])[CH:14]=2)[CH:9]=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 210851781-[Butyl(methyl)amino]isoquinoline-7-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

生成物 1

HCID 210851791-[butyl(methyl)amino]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isoquinoline-7-carboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 1-[butyl(methyl)amino]isoquinoline-7-carboxylic acid (130 mg, 0.5 mmol) and N,N-diisopropylethylamine (525 μL, 3.0 mmol)in methylene chloride (6.25 mL) was added HBTU (190 mg, 0.5 mmol) and the reaction mixture was stirred for 0.5 h. (2R,3S)-3-Amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (174 mg, 0.42 mmol) was added in one portion and the reaction mixture was stirred at room temperature 18 h. The reaction mixture was diluted with methylene chloride and washed with saturated sodium bicarbonate, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 1-5% methanol in chloroform) gave 1-[butyl(methyl)amino]-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}isoquinoline-7-carboxamide

後処理

  1. additionwas added in one portion
  2. washwashed with saturated sodium bicarbonate, and saturated sodium chloride
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography (silica, 1-5% methanol in chloroform)

出典と根拠

ORDレコード
ord-b402bf9e5c6d48d0a858ff696a00ef3d
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

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