Cesium carbonate → N-(4,5-Dihydro-1H-imidazol-2-yl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine

HRID 540069Notes

Reaction equation

HRID 540069 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.[NH:26]1[CH2:30][CH2:29][N:28]=[C:27]1[NH2:31].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[NH:28]1[CH2:29][CH2:30][N:26]=[C:27]1[NH:31][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 1347844,5-Dihydro-1H-imidazol-2-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71255577N-(4,5-Dihydro-1H-imidazol-2-yl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (150 mg, 0.40 mmol, prepared in analogy to the one in Example 2-1), hydrogen iodide salt of 4,5-dihydro-1H-imidazol-2-amine (110 mg, 0.515 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (25 mg, 0.043 mmol), tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol), cesium carbonate (525 mg, 1.6 mmol) and 1,4-dioxane (3 mL) was heated with stirring in a 5 mL of microwave process vial for 2 hours at 120° C. under microwave irradiation. The resulting mixture was filtered and washed with ethyl acetate. The filtrate was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford the product as a solid. MS obsd. (ESI+) [(M+H)+] 422, 1H NMR (400 MHz, CD3OD) δ ppm 7.68-7.59 (m, 2 H), 7.56 (s, 1 H), 7.50-7.41 (m, 2 H), 7.08 (s, 1 H), 5.23 (brs, 2 H), 4.62 (s, 3 H), 3.76 (s, 3 H), 3.61 (t, J=4.93 Hz, 2 H), 2.68 (s, 4 H), 2.45 (s, 2 H).

Workup

  1. temperaturewas heated
  2. filtrationThe resulting mixture was filtered
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-c6a6780dcf0e4dcea58ce628436d19fa
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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