Potassium Carbonate → HCID 178461054, compound

HRID 1943882Notes

Reaction equation

HRID 1943882 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([NH:11][C:12](=[O:28])[C:13]3[C:18]([F:19])=[CH:17][CH:16]=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[C:14]=3[F:27])[CH:9]=2)[NH:4][N:3]=1.[CH3:29][N:30]([CH3:49])[CH2:31][CH2:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=1.C([O-])([O-])=O.[K+].[K+]>CC#N.O.C(OCC)(=O)C.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>[CH3:29][N:30]([CH3:49])[CH2:31][CH2:32][O:33][C:34]1[CH:35]=[C:36]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([NH:11][C:12](=[O:28])[C:13]4[C:18]([F:19])=[CH:17][CH:16]=[C:15]([NH:20][S:21]([CH2:24][CH2:25][CH3:26])(=[O:23])=[O:22])[C:14]=4[F:27])[CH:9]=3)[NH:4][N:3]=2)[CH:37]=[CH:38][CH:39]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 54594420Dimethyl((2-(3-(tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl))amineHCID 178461050HCID 178461050, compound

Product 1

HCID 178461054HCID 178461054, compoundYield 27.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
160 °C

Procedure

Pd(PPh3)4 (0.0075 g, 0.0065 mmol) was added to a suspension of N-(3-bromo-1H-pyrazolo[3,4-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (0.031 g, 0.065 mmol), N,N-dimethyl-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethanamine (0.029 g, 0.098 mmol) and K2CO3 (0.072 g, 0.52 mmol) in MeCN/H2O (4:1, 1 mL). The reaction mixture was heated to 160° C. in a microwave reactor for 30 minutes. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and filtered through GF/F paper. The filter cake was rinsed with ethyl acetate (50 mL). The filtrate was transferred to a separation funnel, and the organic layers were washed with water (3×20 mL). The organic layers were dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with DCM/MeOH (10:1), DCM/MeOH (10:1) containing 1% triethylamine to give N-(3-(3-(2-(dimethylamino)ethoxy)phenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)-2,6-difluoro-3-(propylsulfonamido)benzamide (0.010 g, 27%) as a solid. 1H NMR (400 MHz, CD3OD) δ 9.0 (s, 1H), 8.7 (s, 1H), 7.7 (m, 1H), 7.6 (m, 2H), 7.5 (m, 1H), 7.2 (m, 1H), 7.1 (d, J=7.0 Hz, 1H), 4.3 (t, J=5.2 Hz, 2H), 3.1 (m, 2H), 3.0 (m, 2H), 2.5 (s, 6H), 1.9 (m, 2H), 1.1 (t, J=7.6 Hz, 3H); m/z (APCI-pos) M+1=559.1.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through GF/F paper
  3. washThe filter cake was rinsed with ethyl acetate (50 mL)
  4. customThe filtrate was transferred to a separation funnel
  5. washthe organic layers were washed with water (3×20 mL)
  6. customThe organic layers were dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography
  10. washeluting with DCM/MeOH (10:1), DCM/MeOH (10:1)
  11. additioncontaining 1% triethylamine

Sources & evidence

ORD record
ord-3efabca7e81b46d58a4869e27335fe45
Source dataset
uspto-grants-2013_03
Patent number
US08394795B2

Reaction notes

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