Tetrahydrofuran → HCID 24771241, compound

HRID 631895Notes

Reaction equation

HRID 631895 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([Cl:16])[CH:10]=2)=[N:6][CH:7]=1.N12CCCN=C1CCCCC2.[CH:28]1([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH2:30][CH2:29]1.C1C[O:40][CH2:39]C1>>[Cl:16][C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][C:12]=1[Cl:15])[O:8][C:5]1[N:6]=[CH:7][C:2]([C:39]([N:34]2[CH2:33][CH2:32][N:31]([CH:28]([CH3:29])[CH3:30])[CH2:36][CH2:35]2)=[O:40])=[CH:3][CH:4]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 514889Pyridine, 5-bromo-2-(3,4-dichlorophenoxy)-HCID 47420041-Cyclopropylpiperazine

Product 1

HCID 24771241HCID 24771241, compoundYield 76%

Conditions

Temperature
125 °C

Procedure

To a solution of 5-bromo-2-(3,4-dichloro-phenoxy)-pyridine (0.303 g, 0.949 mmol) in THF (4 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; 0.30 mL, 2.0 mmol), cyclopropyl piperazine (0.30 mL, 2.4 mmol), trans-di-m-acetatobis[2-(di-o-tolylphosphino)benzyl]di-palladium (II) (Hermann's catalyst; 36.7 mg, 0.039 mmol), t-BuPHBF4+ (17.4 mg, 0.060 mmol), and Mo(CO)6 (301 mg, 1.14 mmol). The reaction mixture was heated in the microwave for 6 min at 125° C., cooled to rt, then concentrated. Purification by FCC gave the desired product (284 mg, 76%). MS (ESI): mass calcd. for C19H21Cl2N3O2, 393.10; m/z found, 394.7 [M+H]+. 1H NMR (CDCl3): 8.24 (dd, J=2.5, 0.8 Hz, 1H), 7.83 (dd, J=8.3, 2.5 Hz, 1H), 7.47 (d, J=8.8 Hz, 1H), 7.30 (d, J=2.8 Hz, 1H), 7.03 (dd, J=8.8, 2.5 Hz, 1H), 7.00 (dd, J=8.3, 0.8 Hz, 1H), 3.90-3.40 (br m, 4H), 2.74 (h, J=6.8 Hz, 1H), 2.64-2.43 (br m, 4H), 1.04 (d, J=7.1 Hz, 6H).

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. customPurification by FCC

Sources & evidence

ORD record
ord-f9763f185129492881d37d638307c0d4
Source dataset
uspto-grants-2016_04
Patent number
US09321729B2

Reaction notes

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