2-(Methylamino)ethanol → (e)-3-(5-Cyano-2-methoxy-phenyl)-n-((r)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide

HRID 1797266노트

반응식

HRID 1797266 반응식
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:34][CH3:35])=[C:7](/[CH:9]=[CH:10]/[C:11]([NH:13][C@@H:14]([CH2:19][N:20]2[CH2:25][CH2:24][CH:23]([O:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH2:22][CH2:21]2)[CH2:15][C:16](O)=[O:17])=[O:12])[CH:8]=1)#[N:2].C(N(C(C)C)CC)(C)C.[CH3:45][NH:46][CH2:47][CH2:48][OH:49].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C([O-])(O)=O.[Na+].FC1C=CC(OC2CCN(C[C@@H](C(=C)C(N)=O)CC(=O)N(CCO)C)CC2)=CC=1>CN(C=O)C.C(OC(=O)C)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:34][CH3:35])=[C:7](/[CH:9]=[CH:10]/[C:11]([NH:13][C@H:14]([CH2:15][C:16](=[O:17])[N:46]([CH2:47][CH2:48][OH:49])[CH3:45])[CH2:19][N:20]2[CH2:21][CH2:22][CH:23]([O:26][C:27]3[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=3)[CH2:24][CH2:25]2)=[O:12])[CH:8]=1)#[N:2]

참가 물질

9

반응물 6

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10140715(R)-3-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-4-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-butyric acidHCID 131725718((R)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide

생성물 1

HCID 10280381(e)-3-(5-Cyano-2-methoxy-phenyl)-n-((r)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of (R)-3-[(E)-3-(5-cyano-2-methoxy-phenyl)-acryloylamino]-4-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-butyric acid (0.1 g, 0.21 mmol) in DMF (1 ml) is treated with diisopropylethylamine (0.108 ml, 0.62 mmol) and 2-methylamino-ethanol (0.02 ml, 0.248 mmol). To the solution is added O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (0.117 g, 0.31 mmol) and the reaction mixture stirred at room temperature for 1 hour. The reaction mixture is partioned between ethylacetate and saturated aqueous NaHCO3. The ethylacetate phase is washed with saturated brine, dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution with 5:95 methanol/DCM) to afford (E)-3-(5-cyano-2-methoxy-phenyl)-.N.-((R)-2-[4-(4-fluoro-phenoxy)-piperidin-1-yl]-1-{[(2-hydroxy-ethyl)-methyl-carbamoyl]-methyl}-ethyl)-acrylamide. [M-H] 537.02.

후처리

  1. washThe ethylacetate phase is washed with saturated brine
  2. dry with materialdried over MgSO4
  3. customevaporated
  4. customThe crude product is purified by flash silica chromatography (elution with 5:95 methanol/DCM)
  5. customto afford (E)-3-(5-cyano-2-methoxy-phenyl)-.N

출처 및 근거

ORD 기록
ord-07441c7880a84acc94db9249f453d3ac
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07034042B2

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