1,2-Dichloroethane → HCID 118092730, compound

HRID 2207384Notes

Reaction equation

HRID 2207384 reaction equation
[Cl-].[NH4+].[CH3:3][C:4]1[CH:5]=[C:6]([C:21]2[CH:22]=[CH:23][C:24]([O:27][C:28]3[CH:36]=[CH:35][C:31]([C:32]([OH:34])=O)=[CH:30][CH:29]=3)=[N:25][CH:26]=2)[CH:7]=[C:8]([NH:10][C:11]2[N:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][N:12]=2)[CH:9]=1.C(Cl)CCl.C1C=CC2N(O)N=[N:47]C=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[CH3:3][C:4]1[CH:5]=[C:6]([C:21]2[CH:22]=[CH:23][C:24]([O:27][C:28]3[CH:36]=[CH:35][C:31]([C:32]([NH2:47])=[O:34])=[CH:30][CH:29]=3)=[N:25][CH:26]=2)[CH:7]=[C:8]([NH:10][C:11]2[N:16]=[C:15]([C:17]([F:20])([F:18])[F:19])[CH:14]=[CH:13][N:12]=2)[CH:9]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 118092616HCID 118092616, compound

Product 1

HCID 118092730HCID 118092730, compoundYield 78.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Ammonium chloride (39 mg, 0.733 mmol) was added to a stirred solution of 4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]oxy}benzoic acid (114 mg, 0.244 mmol), EDC (94 mg, 0.489 mmol), HOBt (99 mg, 0.733 mmol), and diisopropylethyl amine (0.256 mL, 1.47 mmol) in DMF (4 mL). The reaction mixture was stirred at room temperature for 16 hours, diluted with water and extracted with ethyl acetate (3×). The combined organics were washed with saturated sodium bicarbonate and then brine. The organic layer was dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (MeOH/DCM) to afford 4-{[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]oxy}benzamide (89 mg, 0.191 mmol) as a white solid. MS ESI calc'd for C24H19F3N5O3 [M+H]+ 466. found 466. 1H NMR (500 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.81 (d, J=5.0 Hz, 1H), 8.39 (d, J=2.0 Hz, 1H), 8.08 (dd, J=8.8, 1.8 Hz, 1H), 7.96 (s, 1H), 7.92 (d, J=8.0 Hz, 2H), 7.89 (s, 1H), 7.53 (s, 1H), 7.34 (s, 1H), 7.26 (d, J=4.5 Hz, 1H), 7.21 (d, J=8.0 Hz, 2H), 7.17 (d, J=8.5 Hz, 1H), 7.15 (s, 1H), 2.34 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washThe combined organics were washed with saturated sodium bicarbonate
  3. dry with materialThe organic layer was dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-b7a0239c63854c4485f3506f65c34006
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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