1,2-Dichloroethane → HCID 57805499, compound

HRID 2064442Notes

Reaction equation

HRID 2064442 reaction equation
[NH:1]([C:3]1[N:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:7]([C:13]1[CH:18]=[CH:17][C:16]([C:19]3([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:22][CH2:21][CH2:20]3)=[CH:15][CH:14]=1)=[N:8]2)[NH2:2].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:31]1([C:6]2[C:7]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:22][CH2:21][CH2:20]4)=[CH:15][CH:14]=3)=[N:8][C:9]3[CH:10]=[CH:11][N:12]4[C:57]([C:52]5[N:53]=[CH:54][CH:55]=[CH:56][N:51]=5)=[N:2][N:1]=[C:3]4[C:4]=3[CH:5]=2)[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

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-3bbbae30d1064954bd47d6339fef2666
Source dataset
uspto-grants-2012_10
Patent number
US08288407B2

Reaction notes

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