Triethylamine → 6-Fluoro-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 541845Notes

Reaction equation

HRID 541845 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]([F: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>[F: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 86636270N-{3-[2-(4-Aminopyridin-2-yl)ethyl]phenyl}-2-chloro-5-fluoropyrimidin-4-amine Dihydrochloride

Product 1

HCID 579621426-Fluoro-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 41%

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-chloro-5-fluoropyrimidin-4-amine dihydrochloride (50.0 mg, 0.12 mmol) and triethylamine (0.05 mL, 0.36 mmol) in dry 1,4-dioxane (1.0 mL) was added (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.16 mg, 0.007 mmol), palladium acetate (1.1 mg, 0.0048 mmol) and cesium carbonate (78.2 mg, 0.24 mmol). The cloudy 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, filtered and concentrated to give the residue, which was then triturated with MeOH/THF/EtOAc to provide the desired product as a white powder (15 mg, 41%). LCMS for C17H15FN5 (M+H)+: m/z=308.0. 1H NMR (400 MHz, DMSO-d6): δ 9.68 (s, 1H), 9.58 (s, 1H), 8.14 (m, 3H), 7.84 (s, 1H), 7.26 (dd, J=15.2, 7.2 Hz, 1H), 7.04 (dd, J=7.2, 2.0 Hz, 2H), 6.84 (dd, J=5.6, 2.0 Hz, 1H), 2.90 (m, 4H).

Workup

  1. customThe cloudy 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
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the residue, which
  8. customwas then triturated with MeOH/THF/EtOAc

Sources & evidence

ORD record
ord-30a3ede25652400c82b4a702fc21bdd1
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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