Triethylamine → 6-Chloro-2,4,8,19,23-pentazatetracyclo[15.3.1.13,7.110,14]tricosa-1(20),3,5,7(23),10(22),11,13,17(21),18-nonaen-13-amine

HRID 1614985Notes

Reaction equation

HRID 1614985 reaction equation
Cl.Cl.Cl.[NH2:4][C:5]1[CH:20]=[CH:19][C:8]([CH2:9][NH:10][C:11]2[C:16]([Cl:17])=[CH:15][N:14]=[C:13](Cl)[N:12]=2)=[CH:7][C:6]=1[CH2:21][CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([NH2:29])[CH:28]=1.C(N(CC)CC)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)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.O1CCOCC1>[Cl:17][C:16]1[CH:15]=[N:14][C:13]2[NH:29][C:27]3[CH:26]=[N:25][CH:24]=[C:23]([CH:28]=3)[CH2:22][CH2:21][C:6]3[CH:7]=[C:8]([CH2:9][NH:10][C:11]=1[N:12]=2)[CH:19]=[CH:20][C:5]=3[NH2:4]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 86643683N-{4-Amino-3-[2-(5-aminopyridin-3-yl)ethyl]benzyl}-2,5-dichloropyrimidin-4-amine trihydrochloride

Product 1

HCID 468647506-Chloro-2,4,8,19,23-pentazatetracyclo[15.3.1.13,7.110,14]tricosa-1(20),3,5,7(23),10(22),11,13,17(21),18-nonaen-13-amineYield 42%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Into a reaction flask were added N-{4-amino-3-[2-(5-aminopyridin-3-yl)ethyl]benzyl}-2,5-dichloropyrimidin-4-amine trihydrochloride (0.29 g, 0.74 mmol), 1,4-dioxane (5 mL), and triethylamine (0.31 mL, 2.2 mmol). The mixture was stirred at rt under N2 for 5 minutes, followed by an addition of palladium acetate (5 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (12.9 mg, 0.02 mmol), and cesium carbonate (500 mg, 2.0 mmol). The reaction mixture was degassed with N2 bubbling. The tube was then sealed and heated at 160° C. for 2 hours. After concentration, the crude product was purified by silica gel column chromatography to give the desired product as a white powder (100 mg, 42%). LCMS for C18H18ClN6 (M+H)+: m/z=353.0. 1H NMR (400 MHz, DMSO-d6): δ 9.65 (s, 1H), 8.44 (d, J=1.6 Hz, 2H), 8.16 (d, J=2.3 Hz, 1H), 8.01 (s, 1H), 7.11 (m, 2H), 7.03 (m, 2H), 6.69 (s, 1H), 4.14 (d, J=5.8 Hz, 2H), 2.88 (m, 4H).

Workup

  1. customThe reaction mixture was degassed with N2 bubbling
  2. customThe tube was then sealed
  3. temperatureheated at 160° C. for 2 hours
  4. concentrationAfter concentration
  5. customthe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1919526a7c4f43f8b162069b0e3339f8
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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