1,2-Dichloroethane → HCID 57805499, compound

HRID 2104123Notes

Reaction equation

HRID 2104123 reaction equation
[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[N:23][C:24]=4[NH:34][NH2:35])[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[N:51]1[CH:56]=[CH:55][CH:54]=[N:53][C:52]=1[C:57](O)=O.CCN(C(C)C)C(C)C.C(O)(=O)C>C(OCC)(=O)C.CN(C=O)C>[C:1]([O:5][C:6](=[O:36])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:27]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:26][C:25]4[C:24]5=[N:34][N:35]=[C:57]([C:52]6[N:53]=[CH:54][CH:55]=[CH:56][N:51]=6)[N:23]5[CH:22]=[CH:21][C:20]=4[N:19]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 12626245Pyrimidine-2-carboxylic acidHCID 57805468Tert-butyl {1-[4-(5-hydrazino-3-phenyl-1,6-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 57805499HCID 57805499, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a round bottom flask was added tert-butyl{1-[4-(5-hydrazino-3-phenyl-1,6-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate (1-6) (267 mg, 0.554 mmol), EDC (138 mg, 0.721 mmol), HOBt (97 mg, 0.721 mmol), pyrimidine-2-carboxylic acid (89 mg, 0.721 mmol), DIPEA (0.367 mL, 2.218 mmol), and DMF (3 mL). The reaction mixture was then capped & heated under microwave irradiation at 100° C. for 5 minutes. The mixture was cooled, acetic acid (0.476 mL, 8.32 mmol) was added and the reaction was then capped & heated under microwave irradiation at 80° C. for 5 minutes. The reaction mixture was permitted to cool to room temperature, suspended in ethyl acetate, washed with a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography 0-10% IPA/DCM. The appropriate fractions were combined and the solvent was removed in vacuo to give tert-butyl{1-[4-(9-phenyl-3-pyrimidin-2-yl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl)phenyl]cyclobutyl}carbamate (1-6d) as an orange solid. MS (M+H)+: observed=570.2, calculated=570.7.

Workup

  1. customThe reaction mixture was then capped
  2. temperatureThe mixture was cooled
  3. customthe reaction was then capped
  4. temperatureheated under microwave irradiation at 80° C. for 5 minutes
  5. temperatureto cool to room temperature
  6. washwashed with a saturated solution of sodium bicarbonate
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by silica gel chromatography 0-10% IPA/DCM
  11. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-349dc6257217407bad12e824cc268c40
Source dataset
uspto-grants-2009_08
Patent number
US07576209B2

Reaction notes

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