Sodium Azide → HCID 178461497, compound

HRID 1868123Notes

Reaction equation

HRID 1868123 reaction equation
[CH3:1][C@H:2]1[N:7]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([OH:23])([CH3:22])[C:18]([F:21])([F:20])[F:19])[CH:12]=2)(=[O:10])=[O:9])[CH2:6][CH2:5][N:4]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=2[C:32]([F:35])([F:34])[F:33])[CH2:3]1.[N-:36]=[N+:37]=[N-:38].[Na+]>C1(C)C=CC=CC=1>[F:19][C:18]([F:21])([F:20])[C:17]([C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([S:8]([N:7]2[CH2:6][CH2:5][N:4]([C:24]3[CH:31]=[CH:30][C:27]([C:28]4[NH:38][N:37]=[N:36][N:29]=4)=[CH:26][C:25]=3[C:32]([F:35])([F:33])[F:34])[CH2:3][C@H:2]2[CH3:1])(=[O:9])=[O:10])[CH:12]=1)([OH:23])[CH3:22]

Participants

4

Reactant 2

HCID 33557Sodium AzideHCID 57418324HCID 57418324, compound

Product 1

HCID 178461497HCID 178461497, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

The compound of Example 29U, 4-((3R)-3-methyl-4-{[3-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl]sulfonyl}piperazin-1-yl)-3-(trifluoromethyl)benzonitrile, was used as starting material to make the title compound. A mixture of 4-((3R)-3-methyl-4-{[3-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl]sulfonyl}piperazin-1-yl)-3-(trifluoromethyl)benzonitrile (300 mg, 0.58 mmol), NaN3 (112.5 mg, 1.73 mmol), Et3NHCl (238.1 mg, 1.73 mmol) were charged to a microwave vial. Toluene (3 mL) was introduced under nitrogen atmosphere and the reaction mixture was heated at 100° C. over night in an oil bath. Reaction was complete as determined by TLC. Reaction mixtures was diluted with EtoAc, washed with 10% HCl until pH=6-7. The organic layer was dried over Na2SO4 and concentrated. The crude product was purified via prep HPLC under acidic condition to yield 1,1,1-trifluoro-2-[3-({(2R)-2-methyl-4-[4-(1H-tetrazol-5-yl)-2-(trifluoromethyl)phenyl]piperazin-1-yl}sulfonyl)phenyl]propan-2-ol as a white solid (111.2 mg, 34.3 yield %). HRMS: calcd for C22H22F6N6O3S+H+, 565.14510. found (ESI-FTMS, [M+H]1+), 565.14524.

Workup

  1. additionwere charged to a microwave vial
  2. customReaction
  3. customReaction mixtures
  4. additionwas diluted with EtoAc
  5. washwashed with 10% HCl until pH=6-7
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified via prep HPLC under acidic condition
  9. customto yield

Sources & evidence

ORD record
ord-600183408532463aa38be4373210a834
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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