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

HRID 1866513Notes

Reaction equation

HRID 1866513 reaction equation
[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]

Participants

7

Reactant 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

Product 1

HCID 690243723-{2-[(2R)-2-(tert-butyldimethylsilanyloxy)-2-(4-hydroxy-3-hydroxymethyl-phenyl)ethylamino]-2-methylpropyl}-N-[2-(4-chlorophenyl)ethyl]benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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]+

Workup

  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)

Sources & evidence

ORD record
ord-590b8449c0bd463b9977c194bafa1303
Source dataset
uspto-grants-2009_12
Patent number
US07629358B2

Reaction notes

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