Diethyl Ether → HCID 178508826, compound

HRID 1631430Notes

Reaction equation

HRID 1631430 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:12]([NH:14][C@H:15]3[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17][CH2:16]3)=[O:13])[CH:9]=[C:10](Br)[N:6]2[N:5]=[CH:4][N:3]=1.[F:22][C:23]1[CH:28]=[C:27](B(O)O)[CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[K+].[K+].CCOCC>CN(C=O)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>[NH2:1][C:2]1[C:7]2=[C:8]([C:12]([NH:14][C@H:15]3[CH2:20][CH2:19][C@H:18]([OH:21])[CH2:17][CH2:16]3)=[O:13])[CH:9]=[C:10]([C:27]3[CH:26]=[CH:25][N:24]=[C:23]([F:22])[CH:28]=3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 178508825HCID 178508825, compound

Product 1

HCID 178508826HCID 178508826, compoundYield 19.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 3A (39 mg, 0.11 mmol), 2-fluoropyridin-4-ylboronic acid (31 mg, 0.22 mmol) and aq. potassium carbonate (0.14 mL, 0.21 mmol) in 2 mL of degassed DMF was treated with 6 mg (0.006 mmol) of tetrakis(triphenylphosphine)palladium(0). The mixture was stirred at 100° C. for 2 h, cooled to RT, and diluted with water. The resulting mixture was extracted three times with 9:1 chloroform-ethanol, and the combined organic extracts dried and concentrated. Trituration from ether afforded 3 (8 mg, 18% yield) as a white powder. HPLC: 5.88 min (YMC S5 ODS, 4.5×50 mm. 4 mL/min, 10-90% methanol-water 0.2% H3PO4, gradient over 12 min). MS (ES): m/z=371 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.49 (br. s, 1H); 8.36-8.44 (m, 3H); 8.16 (s, 1H); 8.15 (s, 1H); 8.01-8.04 (m, 1H); 7.95 (s, 1H); 4.65 (d, 1H, J=4.3 Hz); 3.75-3.86 (m, 1H); 3.40-3.51 (m, 1H); 1.85-1.96 (m, 4H); 1.23-1.49 (m, 4H).

Workup

  1. temperaturecooled to RT
  2. extractionThe resulting mixture was extracted three times with 9:1 chloroform-ethanol
  3. customthe combined organic extracts dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-0dffb1894d5f43a3885ccc2d9d7c6aee
Source dataset
uspto-grants-2014_07
Patent number
US08791257B2

Reaction notes

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