Triethylamine → 6-Chloro-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 541854Notes

Reaction equation

HRID 541854 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]([Cl: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>[Cl: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 86636272N-{3-[2-(2-Aminopyridin-4-yl)ethyl]phenyl}-2,5-dichloropyrimidin-4-amine Dihydrochloride

Product 1

HCID 579626716-Chloro-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 61.8%

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}-2,5-dichloropyrimidin-4-amine dihydrochloride (35.0 mg, 0.08 mmol) and triethylamine (0.034 mL, 0.24 mmol) in a mixed solvent of 1,4-dioxane (0.70 mL) and N,N-dimethylformamide (0.70 mL) at rt were added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.6 mg, 0.010 mmol), palladium acetate (2.2 mg, 0.010 mmol) and cesium carbonate (52.6 mg, 0.16 mmol). The mixture was degassed by bubbling N2 through the solution. The sealed tube was then microwaved at 160° C. for 20 min. The reaction mixture was diluted with THF/MeOH, filtered and concentrated to give a residue, which was triturated with MeOH/EtOAc (1:1) to provide the desired product (16 mg, 61%) as a light brown powder. LCMS for C17H15ClN5 (M+H)+: m/z=324.0. 1H NMR (400 MHz, DMSO-d6): δ 9.44 (s, 1H), 9.22 (s, 1H), 8.18 (m, 1H), 8.06 (m, 1H), 7.86 (m, 1H), 7.68 (m, 1H), 7.40 (m, 1H), 7.28 (m, 1H), 7.05 (m, 1H), 6.28 (m, 1H), 3.05 (m, 4H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling N2 through the solution
  3. customThe sealed tube was then microwaved at 160° C. for 20 min
  4. additionThe reaction mixture was diluted with THF/MeOH
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a residue, which
  8. customwas triturated with MeOH/EtOAc (1:1)

Sources & evidence

ORD record
ord-c8d2eb2096484338a992638861efc974
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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