Azidotrimethylsilane → HCID 178432505, compound

HRID 2381950Notes

Reaction equation

HRID 2381950 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]([NH:13][C:14]([C:16]2[C:17]([CH3:29])=[N:18][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)=[N:20][CH:21]=2)=[O:15])[CH:4]=1)#[N:2].[Si]([N:34]=[N+:35]=[N-:36])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1(C)C=CC=CC=1.CCOC(C)=O>[F:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]([NH:13][C:14]([C:16]1[C:17]([CH3:29])=[N:18][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)=[N:20][CH:21]=1)=[O:15])[CH:4]=[C:3]2[C:1]1[NH:36][N:35]=[N:34][N:2]=1

Participants

6

Reactant 3

HCID 78378AzidotrimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 250996952-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-cyano-5-fluoro-indol-1-yl)-amide

Product 1

HCID 178432505HCID 178432505, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-cyano-5-fluoro-indol-1-yl)-amide (120 mg, 0.31 mmol), TMSN3 (62 μL, 0.465 mmol), and TBAF (0.155 μL, 0.155 mmol, 1 M in THF) in toluene (3 mL) is heated at 80° C. for 18 h. The mixture is cooled, diluted with EtOAc, and washed with 1 M HCl. The organic layer is extracted with Na2CO3. The aqueous layer is acidified to pH ˜3 with 3 N aqueous HCl, extracted with EtOAc The organic layer is separated, dried (Na2SO4), filtered and concentrated in vacuo to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [5-fluoro-3-(1H-tetrazol-5-yl)-indol-1-yl]-amide (100 mg, 75%). MS: 433 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 2.81 (s, 3H), 7.28 (m, 1H), 7.47 (m, 1H), 7.67 (m, 1H), 7.73 (m, 1H), 8.01 (m, 1H), 8.21 (m, 1H), 8.33 (m, 1H), 8.36 (s, 1H), 9.33 (s, 1H). IC50=5 nM.

Workup

  1. temperatureThe mixture is cooled
  2. washwashed with 1 M HCl
  3. extractionThe organic layer is extracted with Na2CO3
  4. extractionextracted with EtOAc The organic layer
  5. customis separated
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-95883e7c71e6434fbe37c150ff9d66eb
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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