Sodium Carbonate → (S)-N-(3-(Dimethylamino)-5-(4-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)methanesulfonamide

HRID 1052620Notes

Reaction equation

HRID 1052620 reaction equation
Br[C:2]1[C:10]2[C:9]([NH:11][C@H:12]([C:14]3[N:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18](=[O:26])[C:17]4=[C:27]([CH3:30])[CH:28]=[CH:29][N:16]4[N:15]=3)[CH3:13])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:3]=1.[CH3:39][N:40]([CH3:61])[C:41]1[CH:42]=[C:43]([NH:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH:44]=[C:45](B2OC(C)(C)C(C)(C)O2)[CH:46]=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O>[CH3:39][N:40]([CH3:61])[C:41]1[CH:42]=[C:43]([NH:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH:44]=[C:45]([C:2]2[C:10]3[C:9]([NH:11][C@H:12]([C:14]4[N:19]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[C:18](=[O:26])[C:17]5=[C:27]([CH3:30])[CH:28]=[CH:29][N:16]5[N:15]=4)[CH3:13])=[N:8][CH:7]=[N:6][C:5]=3[N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:3]=2)[CH:46]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 90103173HCID 90103173, compoundHCID 131736122(S)-2-(1-((5-Bromo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

Product 1

HCID 131736235(S)-N-(3-(Dimethylamino)-5-(4-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl)methanesulfonamideYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

(S)-2-(1-((5-Bromo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (100 mg, 0.17 mmol) was treated with N-(3-(dimethylamino)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (145 mg, 0.43 mmol), bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (42 mg, 0.05 mmol) and sodium carbonate (45 mg, 0.42 mmol) in DME (1.6 ml) and water (0.4 ml). The reaction mixture was submitted to vacuum-argon cycles and stirred at 70° C. for 1.5 h. The reaction mixture was cooled down to room temperature and poured into ice-water, basified with potassium carbonate and extracted with ethyl acetate (×3). The organic phase was successively washed with water and brine, dried over magnesium sulphate, filtered and the solvent evaporated under reduced pressure. The residue was purified by normal phase using SP1® Purification System (0% to 10%, hexane-ethyl acetate) to obtain 89.5 mg (73% yield) of the title compound. Purity: 100%.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. extractionextracted with ethyl acetate (×3)
  3. washThe organic phase was successively washed with water and brine
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe residue was purified by normal phase
  8. custom® Purification System (0% to 10%, hexane-ethyl acetate)

Sources & evidence

ORD record
ord-e4587b052a6e4e7e9d0c258f7ac9e258
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

Loading…