Triethylamine → 6-Fluoro-2,4,8,19,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene

HRID 541857Notes

Reaction equation

HRID 541857 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:9]=[C:8]([CH2:10][CH2:11][C:12]2[CH:13]=[C:14]([NH:18][C:19]3[C:24]([F:25])=[CH:23][N:22]=[C:21](Cl)[N:20]=3)[CH:15]=[CH:16][CH:17]=2)[CH:7]=[CH:6][N:5]=1.C(N(CC)CC)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O.O1CCOCC1>[F:25][C:24]1[CH:23]=[N:22][C:21]2[NH:3][C:4]3[N:5]=[CH:6][CH:7]=[C:8]([CH:9]=3)[CH2:10][CH2:11][C:12]3[CH:13]=[C:14]([NH:18][C:19]=1[N:20]=2)[CH:15]=[CH:16][CH:17]=3

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86636273N-{3-[2-(2-Aminopyridin-4-yl)ethyl]phenyl}-2-chloro-5-fluoropyrimidin-4-amine Dihydrochloride

Product 1

HCID 579617686-Fluoro-2,4,8,19,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaeneYield 30.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of N-{3-[2-(2-aminopyridin-4-yl)ethyl]phenyl}-2-chloro-5-fluoropyrimidin-4-amine dihydrochloride (35.0 mg, 0.084 mmol) and triethylamine (0.035 mL, 0.25 mmol) in a mixed solvent of 1,4-dioxane (0.70 mL) and N,N-dimethylformamide (0.70 mL) were added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.8 mg, 0.01 mmol), palladium acetate (2.3 mg, 0.01 mmol) and cesium carbonate (54.7 mg, 0.17 mmol). The mixture was degassed by bubbling N2 through the solution. The sealed tube was then microwaved at 160° C. for 30 min. The reaction mixture was diluted with THF/MeOH, filtered and concentrated to give the residue, which was purified by silica gel column chromatography to provide the desired product as a white powder (7.8 mg, 30%). LCMS for C17H15FN5 (M+H)+: m/z=308.1. 1H NMR (400 MHz, CD3OD): δ 8.09 (d, J=5.2 Hz, 1H), 8.00 (s, 1H), 7.96 (d, J=4.0 Hz, 1H), 7.81 (d, J=1.6 Hz, 1H), 7.31 (m, 1H), 7.04 (m, 2H), 6.91 (m, 1H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling N2 through the solution
  3. customThe sealed tube was then microwaved at 160° C. for 30 min
  4. additionThe reaction mixture was diluted with THF/MeOH
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the residue, which
  8. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a59d687c970a44f8b56ffd992648c1b1
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

Loading…