1,2-Dichloroethane → N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-N'-[(2S,3R)-1-(3,5-difluorophenyl)-4-[[1-(3-ethylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]butanediamide;formic acid

HRID 14332

反応式

HRID 14332 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([F:33])[CH:32]=1)[CH2:5][C@H:6]([NH:22][C:23](=[O:29])[CH2:24][CH2:25][C:26]([OH:28])=[O:27])[C@H:7]([OH:21])[CH2:8][NH:9][C:10]1([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=2)[CH2:12][CH2:11]1.[CH2:34](Cl)[CH2:35]Cl.[CH:38]1[CH:39]=C[C:41]2[N:46](O)N=[N:44][C:42]=2[CH:43]=1>CN(C=O)C>[N:46]12[CH2:35][CH2:34][CH:43]([CH2:38][CH2:39]1)[C@H:42]([NH:44][C:26](=[O:28])[CH2:25][CH2:24][C:23]([NH:22][C@@H:6]([CH2:5][C:4]1[CH:30]=[C:31]([F:33])[CH:32]=[C:2]([F:1])[CH:3]=1)[C@H:7]([OH:21])[CH2:8][NH:9][C:10]1([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][CH3:20])[CH:14]=3)[CH2:12][CH2:11]1)=[O:29])[CH2:41]2.[CH:26]([OH:28])=[O:27]

参加物

5

反応物 3

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 575121114-[((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl)amino}-2-hydroxypropyl)amino]-4-oxobutanoic acid

生成物 1

HCID 86594206N-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-N'-[(2S,3R)-1-(3,5-difluorophenyl)-4-[[1-(3-ethylphenyl)cyclopropyl]amino]-3-hydroxybutan-2-yl]butanediamide;formic acid収率 149.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
45 °C

実験手順

To a solution of R-aminoquinuclidine (0.086 g, 0.434 mmol) TEA (0.302 ml, 2.17 mmol), and anhydrous DMF (2.5 ml) was added 4-[((1S,2R)-1-(3,5-difluorobenzyl)-3-{[1-(3-ethylphenyl)cyclopropyl]amino}-2-hydroxypropyl)amino]-4-oxobutanoic acid (0.200 g, 0.434 mmol), EDC (0.125 g, 0.651 mmol), and HOBT (0.088 g, 0.651 mmol) under nitrogen, with stirring at 45° C. overnight. Reaction mixture was quenched with 10% sodium bicarbonate (aq.) then extracted with ethyl acetate then concentrated in vacuo, yielding product (0.200 g). Prep-HPLC yielded the product as its formate salt. (ES+: 569.3)

後処理

  1. customReaction mixture
  2. customwas quenched with 10% sodium bicarbonate (aq.)
  3. extractionthen extracted with ethyl acetate
  4. concentrationthen concentrated in vacuo

出典と根拠

ORDレコード
ord-2333b7cf0c3441a087984319d431d95b
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

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