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

반응식

HRID 1797271 반응식
[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]

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-a4efb02a2a564838af9b4212ee5e93b8
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07034042B2

연결된 노트

불러오는 중…