1,4-Dioxane hydrochloride → HCID 54589424, compound

HRID 929961Notes

Reaction equation

HRID 929961 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11](=[O:42])[NH:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]3[CH:27]=[C:26]([O:28][CH:29]4[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]4)[CH:25]=[CH:24][N:23]=3)=[O:21])=[CH:15][CH:14]=2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[ClH:43].O1CCOCC1>CC#N>[ClH:43].[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11](=[O:42])[NH:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:21])[C:22]3[CH:27]=[C:26]([O:28][CH:29]4[CH2:30][CH2:31][NH:32][CH2:33][CH2:34]4)[CH:25]=[CH:24][N:23]=3)=[CH:15][CH:14]=2)[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 67125913HCID 67125913, compound

Product 1

HCID 54589424HCID 54589424, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

tert-Butyl 4-(2-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenylcarbamoyl)pyridin-4-yloxy)piperidine-1-carboxylate from Step 3 (280 mg, 0.48 mmol) was stirred in 4N HCl/1,4-Dioxane (10 mL) for 2 h at rt. LC-MS indicated that the reaction was complete. The reaction mixture was diluted with CH3CN (20 mL) and evaporated under reduced pressure. The residue was taken up in CH3CN/Et2O (1:5, v/v), sonicated at rt for 15 min, and filtered to give N-(4-(3-(5-tert-butylisoxazol-3-yl)ureido)phenyl)-4-(piperidin-4-yloxy)picolinamide hydrochloride as a yellow solid (190 mg, 77% yield). LC-MS (ESI) m/z 479 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 10.78 (s, 1H), 9.69 (s, 1H), 9.36 (br. s., 1H), 9.07 (br. s., 1H), 8.60 (d, J=5.84 Hz, 1H), 7.97 (br. s., 1H), 7.83 (d, J=8.85 Hz, 2H), 7.46 (d, J=9.04 Hz, 2H), 7.39 (dd, J=2.17, 5.75 Hz, 1H), 6.51 (s, 1H), 5.07 (br. s., 1H), 4.50 (br. s., 1H), 3.25 (br. s., 2H), 3.13 (d, J=3.58 Hz, 2H), 2.20 (d, J=14.32 Hz, 2H), 1.93 (d, J=9.04 Hz, 2H), 1.30 (s, 9H).

Workup

  1. customevaporated under reduced pressure
  2. customv/v), sonicated at rt for 15 min
  3. filtrationfiltered

Sources & evidence

ORD record
ord-4effa0037d7a4f9e899da7006343f18d
Source dataset
uspto-grants-2016_03
Patent number
US09296722B2

Reaction notes

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