Ammonium formate → HCID 86275388, compound

HRID 626602Notes

Reaction equation

HRID 626602 reaction equation
C([N:8]1[CH2:13][CH2:12][N:11]([C:14]([NH:16][C:17]2[CH:22]=[C:21]([O:23][C:24]3[CH:25]=[N:26][C:27]([NH:30][C:31]([NH:33][C:34](=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36])=[O:32])=[CH:28][CH:29]=3)[CH:20]=[CH:19][N:18]=2)=[O:15])[CH2:10][CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CO.[Pd]>[NH3:8].[C:34]([NH:33][C:31](=[O:32])[NH:30][C:27]1[N:26]=[CH:25][C:24]([O:23][C:21]2[CH:20]=[CH:19][N:18]=[C:17]([NH:16][C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[O:15])[CH:22]=2)=[CH:29][CH:28]=1)(=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36]

Participants

6

Reactant 2

HCID 2723923Ammonium formateHCID 90410317HCID 90410317, compound

Product 2

HCID 222AmmoniaYield 0%HCID 86275388HCID 86275388, compoundYield 105.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

4-Benzyl-N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperazine-1-carboxamide (0.151 g, 0.284 mmol), 10% Pd/C (50% H2O, 0.121 g, 0.057 mmol) and ammonium formate (0.054 g, 0.852 mmol) were combined in MeOH (5 mL) and stirred with heating at 70° C. After 2 h, the reaction was cooled to RT and filtered through diatomaceous earth. The cake was washed well with MeOH and the combined filtrates were concentrated to afford crude product (0.11 g). This was purified by silica gel chromatography (10% MeOH/CH2Cl2; then 0-10% 7M NH3 in MeOH/CH2Cl2) to afford N-(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)piperazine-1-carboxamide (66 mg; 53%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.22 (s, 1H), 10.44 (s, 1H), 9.18 (s, 1H), 8.23 (d, J=2.9 Hz, 1H), 8.11 (d, J=5.7 Hz, 1H), 8.08 (d, J=9.0 Hz, 1H), 7.71 (dd, J=9.0, 2.9 Hz, 1H), 7.36 (d, J=2.4 Hz, 1H), 6.61 (dd, J=5.7, 2.4 Hz, 1H), 3.33-3.31 (m, 4H), 2.63 (t, J=4.9 Hz, 4H), 2.47 (m, 1H), 1.21 (s, 9H); MS (ESI) m/z: 442.2 (M+H+).

Workup

  1. temperaturethe reaction was cooled to RT
  2. filtrationfiltered through diatomaceous earth
  3. washThe cake was washed well with MeOH
  4. concentrationthe combined filtrates were concentrated
  5. customto afford crude product (0.11 g)
  6. customThis was purified by silica gel chromatography (10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-13b1582026c848fc91ce938ec67de340
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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