Sodium Carbonate → (S)-N-(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)pyridin-3-yl)methanesulfonamide

HRID 1052528Notes

Reaction equation

HRID 1052528 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.CC1(C)C(C)(C)OB([C:47]2[CH:48]=[C:49]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:50]=[N:51][CH:52]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[NH4+]>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:30][C:27]1[CH:28]=[CH:29][N:16]2[C:17]=1[C:18](=[O:26])[N:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]([C@@H:12]([NH:11][C:9]1[C:10]3[C:2]([C:47]4[CH:48]=[C:49]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:50]=[N:51][CH:52]=4)=[CH:3][N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:5]=3[N:6]=[CH:7][N:8]=1)[CH3:13])=[N:15]2

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 25517Ammonium ChlorideHCID 53256647N-[5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]methanesulfonamideHCID 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 131736185(S)-N-(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)pyridin-3-yl)methanesulfonamideYield 45%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °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 (75 mg, 0.13 mmol) was dissolved in 1.9 mL N,N-dimethylformamide. N-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamide (225 mg, 0.76 mmol) and sodium carbonate (86 mg, 0.81 mmol) were added and the mixture was submitted to three vacuum-argon cycles. Tetrakis(triphenylphosphine)palladium(0) (44 mg, 0.04 mmol) was added under argon conditions. The mixture was stirred at 130° C. during 1.5 h. The reaction was poured into a saturated ammonium chloride solution and extracted twice with ethyl acetate. The organics were combined and washed with water, brine, dried over sodium sulphate, filtered and evaporated under reduced pressure. The residue was purified using SP1® Purification System (0% to 100%, hexane-ethyl acetate) to give 53 mg (45% yield, 73% purity) of the title compound.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washwashed with water, brine
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe residue was purified
  7. customSP1® Purification System (0% to 100%, hexane-ethyl acetate)

Sources & evidence

ORD record
ord-e319ab670f4741a4965c80acb77c16b9
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

Loading…