Ammonium Hydroxide → 2,2,2-trifluoro-1-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}ethanol

HRID 1520087Notes

Reaction equation

HRID 1520087 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:13])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][N:17]=1)#[CH:15].[N-:25]=[N+:26]=[N-:27].[Na+].CN[C@@H]1CCCC[C@H]1NC.[NH4+].[OH-]>CS(C)=O.O.[Cu](I)I>[F:10][C:9]([F:12])([F:11])[CH:8]([C:5]1[CH:6]=[CH:7][C:2]([N:25]2[CH:15]=[C:14]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[NH:18][N:17]=3)[N:27]=[N:26]2)=[CH:3][CH:4]=1)[OH:13]

Participants

9

Reactant 5

HCID 14923Ammonium HydroxideHCID 33557Sodium AzideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 112190241-(4-Bromophenyl)-2,2,2-trifluoroethanolHCID 178437996HCID 178437996, compound

Product 1

HCID 574051722,2,2-trifluoro-1-{4-[4-(1H-indazol-3-yl)-1H-1,2,3-triazol-1-yl]phenyl}ethanolYield 26.3%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(4-bromophenyl)-2,2,2-trifluoroethan-1-ol (296 mg; 1.16 mmol; 1.1 eq.), 3-Ethynyl-1H-indazole (150 mg; 1.06 mmol; 1.0 eq.), sodium azide (75 mg; 1.16 mmol; 1.1 eq.), D-(−)-isoascorbic acid sodium salt (21 mg; 0.11 mmol; 0.1 eq.), copper iodide (20 mg; 0.11 mmol; 0.1 eq.) and trans-1,2-bis(methylamino)cyclohexane (22 mg; 0.16 mmol; 0.15 eq.) in DMSO (2.6 mL) and WATER (0.5 mL) was heated in a sealed tube at 70° C. for 48 h. The reaction mixture was poured into a solution of saturated NH4OH and extracted with DCM (twice). Combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by preparative HPLC gave the title compound as a beige solid (100 mg, 26%). 1H NMR (DMSO) δ 13.38 (brs, 1H), 9.33 (s, 1H), 8.36 (dt, J=8.0 Hz, 1.0 Hz, 1H), 8.12 (d, J=8.7 Hz, 2H), 7.75 (d, J=8.7 Hz, 2H), 7.61 (dt, J=8.4 Hz, 1.0 Hz, 1H), 7.47-7.42 (m, 1H), 7.29-7.23 (m, 1H), 7.05 (bs, 1H), 5.34 (q, J=7.2 Hz, 1H). HPLC (max plot) 100.0%; Rt %3.83 min. UPLC/MS: (MS+) 360.4, (MS−) 358.4.

Workup

  1. extractionextracted with DCM (twice)
  2. washCombined organic phases were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-afdf69e5f1a44011bc6b65118056f903
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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