Water → (S)-1-[2-hydroxy-4-(4-{hydroxy-[3-(1H-tetrazol-5-yl)-phenyl]-methyl}-benzylsulfanyl)-3-propyl-phenyl]-ethanone

HRID 1161036Notes

Reaction equation

HRID 1161036 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[C:5]([C:8]1[CH:13]=[CH:12][C:11]([S:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C@H:22]([OH:31])[C:23]3[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=3)[C:26]#[N:27])=[CH:18][CH:17]=2)=[C:10]([CH2:32][CH2:33][CH3:34])[C:9]=1[OH:35])(=[O:7])[CH3:6].O>CN1CCCC1=O.[Br-].[Zn+2].[Br-]>[OH:35][C:9]1[C:10]([CH2:32][CH2:33][CH3:34])=[C:11]([S:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C@H:22]([OH:31])[C:23]3[CH:30]=[CH:29][CH:28]=[C:25]([C:26]4[NH:27][N:3]=[N:2][N:1]=4)[CH:24]=3)=[CH:18][CH:17]=2)[CH:12]=[CH:13][C:8]=1[C:5](=[O:7])[CH3:6]

Participants

6

Reactant 3

HCID 962WaterHCID 33557Sodium AzideHCID 66699627(S)-3-{[4-(4-Acetyl-3-hydroxy-2-propyl-phenylsulfanylmethyl)-phenyl]-hydroxy-methyl}-benzonitrile

Product 1

HCID 178439801(S)-1-[2-hydroxy-4-(4-{hydroxy-[3-(1H-tetrazol-5-yl)-phenyl]-methyl}-benzylsulfanyl)-3-propyl-phenyl]-ethanoneYield 31.2%

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

Add sodium azide (66 mg, 0.25 mmol) and zinc bromide (131 mg, 0.50 mmol) to a solution of (S)-3-{[4-(4-Acetyl-3-hydroxy-2-propyl-phenylsulfanylmethyl)-phenyl]-hydroxy-methyl}-benzonitrile (110 mg, 0.25 mmol) in N-methylpyrrolidinone (2.0 ml). Heat the mixture at 140° C. for 12 hours, then cool to room temperature and stir for 18 hours. Pour the mixture into water (25 ml) and stir the solid suspension for 20 minutes. Filter and wash the filtered solid with water. Dissolve the solid in a 1N HCl (25 ml) and ethyl acetate (20 ml) mixture. Extract the aqueous layer with ethyl acetate (25 ml), combine the organic extracts, then wash with water, brine, dry over sodium sulfate and concentrate. Purify the crude product via reverse phase HPLC using a gradient of 90:10 to 20:80 (water/0.1% TFA):acetonitrile as eluent to give the title compound (37 mg, 31%). MS (m/z) 473 (M−H). 1H NMR (400 MHz, DMSO-d6) 12.83 (s, 1H), 8.13-8.11 (m, 1H), 7.89-7.86 (m, 1H), 7.72 (d, 1H), 7.59-7.51 (m, 2H), 7.41-7.37 (m, 4H), 6.96 (d, 1H), 5.60 (s, 1H), 4.30 (s, 2H), 2.65-2.60 (m, 5H), 1.45 (sextet, 2H), 0.90 (t, 3H).

Workup

  1. temperaturecool to room temperature
  2. stirringstir the solid suspension for 20 minutes
  3. filtrationFilter
  4. washwash the filtered solid with water
  5. dissolutionDissolve the solid in a 1N HCl (25 ml) and ethyl acetate (20 ml) mixture
  6. extractionExtract the aqueous layer with ethyl acetate (25 ml)
  7. washwash with water, brine
  8. dry with materialdry over sodium sulfate
  9. concentrationconcentrate
  10. customPurify the crude product via reverse phase HPLC

Sources & evidence

ORD record
ord-267862b2e2374fe38afec850e15ef457
Source dataset
uspto-grants-2010_10
Patent number
US07816523B2

Reaction notes

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