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Triethylamine → 3-{2-[(2R)-2-(tert-butyldimethylsilanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}-N-[2-(4-chlorophenyl)ethyl]benzamide

HRID 1866513
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HRID 1866513 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH2:10])=[CH:4][CH:3]=1.Cl.CN(C)CCCN=C=NCC.[Si:23]([O:30][C@H:31]([C:47]1[CH:52]=[CH:51][C:50]([OH:53])=[C:49]([CH2:54][OH:55])[CH:48]=1)[CH2:32][NH:33][C:34]([CH3:46])([CH3:45])[CH2:35][C:36]1[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=1)[C:39](O)=[O:40])([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[Si:23]([O:30][C@H:31]([C:47]1[CH:52]=[CH:51][C:50]([OH:53])=[C:49]([CH2:54][OH:55])[CH:48]=1)[CH2:32][NH:33][C:34]([CH3:46])([CH3:45])[CH2:35][C:36]1[CH:37]=[C:38]([CH:42]=[CH:43][CH:44]=1)[C:39]([NH:10][CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)=[O:40])([C:26]([CH3:27])([CH3:28])[CH3:29])([CH3:25])[CH3:24]
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참가 물질

7

반응물 5

HCID 8471TriethylamineHCID 674302-(4-Chlorophenyl)ethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 579783093-{2-[(2R)-2-(tert-butyldimethyl silanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}benzoic acid

생성물 1

HCID 69024372
3-{2-[(2R)-2-(tert-butyldimethylsilanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}-N-[2-(4-chlorophenyl)ethyl]benzamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

2-(4-Chlorophenyl)ethylamine (164 mg, 1.06 mmol) was added to a mixture of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (203 mg, 1.06 mmol), 3-{2-[(2R)-2-(tert-butyldimethylsilanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}benzoic acid (Preparation 37) (500 mg, 1.06 mmol), 1-hydroxybenzotriazole hydrate (160 mg, 1.06 mmol) and triethylamine (440 □l, 3.20 mmol) in dichloromethane (30 ml). The resulting solution was stirred for 48 hours under nitrogen. The solvent was removed in vacuo and the residue taken up in ethyl acetate (30 ml), washed with water (20 ml), sodium hydrogen carbonate (0.5 M, 2×20 ml), brine (2×20 ml), dried (sodium sulfate) and the solvent removed in vacuo. The residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume) to furnish the title compound, the resulting material was taken up in methanol and evaporated, then taken up in diethylether and evaporated to yield a white foam (480 mg). 1H NMR (400 MHz, CD3OD) δ=7.64-7.60 (2H, m), 7.36-7.19 (7H, m), 7.05 (1H, dd), 6.72 (1H, d), 4.71-4.67 (1H, m), 4.60 (2H, dd), 3.57 (2H, t), 2.93-2.61 (6H, m), 1.09 (3H, s), 1.06 (3H, s), 0.78 (9H, s), −0.04 (3H, s), −0.22 (3H, s). LRMS (electrospray) m/z 611 [M+H]+, 633 [M+Na]+

후처리

  1. customThe solvent was removed in vacuo
  2. washwashed with water (20 ml), sodium hydrogen carbonate (0.5 M, 2×20 ml), brine (2×20 ml)
  3. dry with materialdried (sodium sulfate)
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel eluting with dichloromethane:methanol:ammonia (95:5:0.5 by volume)

출처 및 근거

ORD 기록
ord-590b8449c0bd463b9977c194bafa1303
출처 데이터셋
uspto-grants-2009_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07629358B2

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