Potassium Carbonate → HCID 131735899, compound

HRID 2207386Notes

Reaction equation

HRID 2207386 reaction equation
Cl.[NH2:2][OH:3].C(=O)([O-])[O-].[K+].[K+].[CH3:10][C:11]1[CH:12]=[C:13]([C:28]2[CH:29]=[CH:30][C:31]([CH2:34][CH2:35][C:36]#[N:37])=[N:32][CH:33]=2)[CH:14]=[C:15]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:16]=1>C(O)C>[OH:3][N:2]=[C:36]([NH2:37])[CH2:35][CH2:34][C:31]1[CH:30]=[CH:29][C:28]([C:13]2[CH:14]=[C:15]([NH:17][C:18]3[N:23]=[C:22]([C:24]([F:26])([F:25])[F:27])[CH:21]=[CH:20][N:19]=3)[CH:16]=[C:11]([CH3:10])[CH:12]=2)=[CH:33][N:32]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 118103376HCID 118103376, compound

Product 1

HCID 131735899HCID 131735899, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

Hydroxylamine hydrochloride (147 mg, 2.11 mmol) and potassium carbonate (292 mg, 2.11 mmol) were added to 3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propanenitrile (135 mg, 0.352 mmol) in ethanol (587 μL). The reaction mixture was heated to 80° C. overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resultant reside was diluted with dichloromethane (2.00 mL), filtered through a short silica get pad and was concentrated under reduced pressure to yield crude N′-hydroxy-3-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]propanimidamide. The crude oxime was diluted with dioxane (1.00 mL) and CDI (57.1 mg, 0.352 mmol), then DBU (106 μL, 0.704 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours, concentrated under reduced pressure, diluted with 1:1 DMSO:methanol (2.00 mL) and filtered. The residue was direct purification by reverse phase chromatography (10-80% MeCN in water+0.5% TFA, linear gradient) to yield 3-{2-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]ethyl}-1,2,4-oxadiazol-5(4H)-one as the TFA salt. MS APCI calc'd for C21H18F3N6O2 [M+H]+ 443. found 443. 1H NMR (500 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.87-8.71 (m, J=18.2 Hz, 2H), 8.11-8.00 (m, 1H), 7.96 (s, 1H), 7.56 (s, 1H), 7.53-7.44 (m, 1H), 7.28 (d, 1H), 7.21 (s, 1H), 3.16 (t, 2H), 2.99 (t, 2H), 2.36 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionThe resultant reside was diluted with dichloromethane (2.00 mL)
  4. filtrationfiltered through a short silica
  5. customget pad
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-a2a11708648145a08c3e98d22edda979
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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