Water → Ammonia

HRID 1433246Notes

Reaction equation

HRID 1433246 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:36]=[CH:35][C:7]([O:8][CH2:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([C@@H:19]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:20][CH2:21][N:22]([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])[CH:13]=2)=[CH:6][CH:5]=1.[CH2:37]([O:44][C:45]1[CH:50]=[CH:49][C:48]([C@@H:51]([O:54][Si:55]([C:58]([CH3:61])([CH3:60])[CH3:59])([CH3:57])[CH3:56])[CH2:52]Br)=[CH:47][C:46]=1[NH:62][S:63]([CH3:66])(=[O:65])=[O:64])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(OCC)(=O)C.O>CS(C)=O>[NH3:1].[CH2:37]([O:44][C:45]1[CH:50]=[CH:49][C:48]([C@@H:51]([O:54][Si:55]([C:58]([CH3:59])([CH3:61])[CH3:60])([CH3:57])[CH3:56])[CH2:52][NH:1][CH2:2][CH2:3][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH2:9][CH2:10][CH2:11][C:12]3[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([C@@H:19]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:20][CH2:21][N:22]([CH:26]([CH3:27])[CH3:28])[CH:23]([CH3:25])[CH3:24])[CH:13]=3)=[CH:35][CH:36]=2)=[CH:47][C:46]=1[NH:62][S:63]([CH3:66])(=[O:64])=[O:65])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 46938715N-{2-(benzyloxy)-5-[(1R)-2-bromo-1-([tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanesulfonamideHCID 579331574-{3-[4-(2-aminoethyl)phenoxy]propyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol

Product 2

HCID 222AmmoniaHCID 57933186N-{2-(benzyloxy)-5-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({2-[4-(3-{3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]-4-hydroxyphenyl}propoxy)phenyl]ethyl}amino)ethyl]phenyl}methanesulfonamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

4-{3-[4-(2-aminoethyl)phenoxy]propyl}-2-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenol (Preparation 8, 134 mg, 0.27 mmol) and N-{2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanesulfonamide (Prepared according to WO2005/080324, 145 mg, 0.28 mmol) were heated at 90° C. in dimethylsulfoxide (0.5 ml) for 24 hours. Ethyl acetate (20 ml) and water (10 ml) were added and the organics separated. The aqueous was washed with ethyl acetate (20 ml) and the combined organics washed with brine (10 ml), dried (magnesium sulphate) and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (80/20/2.0 by volume) to furnish the title compound as a glass, 101 mg.

Workup

  1. washThe aqueous was washed with ethyl acetate (20 ml)
  2. washthe combined organics washed with brine (10 ml)
  3. dry with materialdried (magnesium sulphate)
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by column chromatography on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-1daf65f8d1054da6bbd27128ecc741bf
Source dataset
uspto-grants-2009_11
Patent number
US07612084B2

Reaction notes

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