Triethylamine → 6-Chloro-2,4,8,17,22-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 541841Notes

Reaction equation

HRID 541841 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:9]=[CH:8][N:7]=[C:6]([CH2:10][CH2:11][C:12]2[CH:13]=[C:14]([NH:18][C:19]3[C:24]([Cl:25])=[CH:23][N:22]=[C:21](Cl)[N:20]=3)[CH:15]=[CH:16][CH:17]=2)[CH: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+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:25][C:24]1[CH:23]=[N:22][C:21]2[NH:3][C:4]3[CH:9]=[CH:8][N:7]=[C:6]([CH:5]=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

7

Reactant 4

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86636269N-{3-[2-(4-Aminopyridin-2-yl)ethyl]phenyl}-2,5-dichloropyrimidin-4-amine Dihydrochloride

Product 1

HCID 579623846-Chloro-2,4,8,17,22-pentaazatetracyclo[14.3.1.1(3,7).1(9,13)]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaeneYield 36%

Reagents, catalysts & solvents 2

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

Procedure

To a mixture of N-{3-[2-(4-aminopyridin-2-yl)ethyl]phenyl}-2,5-dichloropyrimidin-4-amine dihydrochloride (90.0 mg, 0.21 mmol) and triethylamine (0.087 mL, 0.62 mmol) in dry 1,4-dioxane (1.8 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (7.2 mg, 0.013 mmol), palladium acetate (1.9 mg, 0.008 mmol) and cesium carbonate (135 mg, 0.42 mmol). The mixture was degassed by bubbling N2 through the solution. The sealed tube was then microwaved at 150° 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 (24 mg, 36%) as a white powder. LCMS for C17H15ClN5 (M+H)+: m/z=324.0. 1H NMR (400 MHz, DMSO-d6): δ 9.69 (s, 1H), 9.28 (s, 1H), 8.15 (m, 3H), 7.74 (d, J=1.6 Hz, 1H), 7.27 (dd, J=16.0, 8.0 Hz, 1H), 7.07 (dd, J=12.4, 3.2 Hz, 2H), 6.84 (dd, J=5.6, 2.0 Hz, 1H), 2.93 (m, 4H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling N2 through the solution
  3. customThe sealed tube was then microwaved at 150° 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-3c965a45c56b4ddba4f835fd8164e3d0
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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