Diisopropylethylamine → {(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester

HRID 1797271

反応式

HRID 1797271 の反応式
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:14][CH3:15])=[C:7](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)[CH:8]=1)#[N:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=C[CH:28]=[CH:29][C:24]=2N=N1.[CH:38](N(C(C)C)CC)(C)C.[NH2:47][C@@H:48]([CH2:54][N:55]1[CH2:60][CH2:59][CH:58]([O:61][C:62]2[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=2)[CH2:57][CH2:56]1)[CH2:49][NH:50][C:51](=[O:53])[OH:52]>C(Cl)Cl>[C:29]([O:53][C:51](=[O:52])[NH:50][CH2:49][C@@H:48]([NH:47][C:11](=[O:13])/[CH:10]=[CH:9]/[C:7]1[CH:8]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]=1[O:14][CH3:15])[CH2:54][N:55]1[CH2:56][CH2:57][CH:58]([O:61][C:62]2[CH:67]=[CH:66][C:65]([F:68])=[CH:64][CH:63]=2)[CH2:59][CH2:60]1)([CH3:28])([CH3:24])[CH3:38]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11458357(E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acidHCID 86759989{(R)-2-Amino-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid

生成物 1

HCID 68576228{(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (0.36 g, 1.77 mmol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium tetrafluoroborate (1.01 g, 2.65 mmol) and diisopropylethylamine (0.46 ml, 2.65 mmol) in DCM (15 ml) is treated with a solution of {(R)-2-Amino-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid .tert.-butyl ester (0.65 g, 1.77 mmol) in DCM (5 ml). The reaction mixture is stirred at ambient temperature for 30 minutes, then washed with saturated aqueous NaHCO3, water and brine. The DCM phase is dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 2% methanol in DCM) to afford {(R)-2-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-3-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-propyl}-carbamic acid tert-butyl ester. [MH]+ 553.0.

後処理

  1. washwashed with saturated aqueous NaHCO3, water and brine
  2. dry with materialThe DCM phase is dried over MgSO4
  3. customevaporated
  4. customThe crude product is purified by flash silica chromatography (elution with 2% methanol in DCM)

出典と根拠

ORDレコード
ord-a4efb02a2a564838af9b4212ee5e93b8
出典データセット
uspto-grants-2006_04
特許番号
US07034042B2

関連ノート

読み込み中…