Dimethylformamide → HCID 86659961, compound

HRID 1907807Notes

Reaction equation

HRID 1907807 reaction equation
Cl[C:2]1[CH:3]=[C:4]([NH:9][CH:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)[C:5](=[O:8])[NH:6][N:7]=1.[C:23]([C:27]1[N:28]=[CH:29][C:30]([C:33]([NH:35][C:36]2[CH:41]=[C:40](B3OC(C)(C)C(C)(C)O3)[CH:39]=[CH:38][C:37]=2[F:51])=[O:34])=[N:31][CH:32]=1)([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].CN(C=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.O.O1CCOCC1>[C:23]([C:27]1[N:28]=[CH:29][C:30]([C:33]([NH:35][C:36]2[CH:41]=[C:40]([C:2]3[CH:3]=[C:4]([NH:9][CH:10]4[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]4)[C:5](=[O:8])[NH:6][N:7]=3)[CH:39]=[CH:38][C:37]=2[F:51])=[O:34])=[N:31][CH:32]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 58540023HCID 58540023, compoundHCID 58540168HCID 58540168, compound

Product 1

HCID 86659961HCID 86659961, compoundYield 36.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
125 °C

Procedure

In a 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser, 10b (500 mg, 1.52 mmol), 5-tert-Butyl-N-(2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazine-2-carboxamide (600 mg, 1.50 mmol) and sodium carbonate (320 mg, 3.01 mmol) were mixed with DMF (8 mL), dioxane (5 mL) and water (2 mL). This mixture was degassed with nitrogen for 30 min. Tetrakis(triphenylphosphine)palladium (175 mg, 0.151 mmol) was added and the mixture was refluxed at 125° C. (bath temperature) for 14 h. The reaction mixture was then cooled to room temperature, and water (100 mL) was added. The resulting precipitate was filtered, and the filter cake was washed with water (250 mL). The filter cake was purified using a silica gel column eluting the desired product with 4-6% methanol in methylene chloride to afford a 36% yield (310 mg) of 10d as a off-white solid: mp 120-121° C.; 1H NMR (500 MHz, CDCl3) δ 10.13 (s, 1H), 10.02 (s, 1H), 9.39 (s, 1H), 8.99 (d, 1H, J=7.5 Hz), 8.68 (s, 1H), 7.56 (br s, 1H), 7.22 (m, 1H), 6.88 (s, 1H), 5.15 (s, 1H), 3.85 (s, 1H), 3.64 (m, 1H), 3.50 (m, 3H), 1.92-1.82 (m, 3H, 1.71 (m, 1H), 1.42 (br s, 1811); MS (APCI+) m/z 566.9 (M+H).

Workup

  1. customIn a 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. temperaturereflux condenser
  3. customThis mixture was degassed with nitrogen for 30 min
  4. temperatureThe reaction mixture was then cooled to room temperature
  5. filtrationThe resulting precipitate was filtered
  6. washthe filter cake was washed with water (250 mL)
  7. customThe filter cake was purified
  8. washeluting the desired product with 4-6% methanol in methylene chloride

Sources & evidence

ORD record
ord-91dc8f7be2474a148621a8e51a9a1158
Source dataset
uspto-grants-2013_12
Patent number
US08598174B2

Reaction notes

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