Pyridine → HCID 86274904, compound

HRID 626581Notes

Reaction equation

HRID 626581 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[NH2:14][C:15]1[N:20]=[C:19]([CH3:21])[C:18]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:31])[CH:24]=2)=[CH:17][CH:16]=1.N1C=CC=CC=1>ClCCCl.C1COCC1>[CH3:21][C:19]1[C:18]([O:22][C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:30]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:31])[CH:24]=2)=[CH:17][CH:16]=[C:15]([NH:14][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])[N:20]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90410027HCID 90410027, compound

Product 1

HCID 86274904HCID 86274904, compoundYield 17.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 2,2,2-trimethylacetamide (0.297 g, 2.94 mmol) in DCE (5 mL) was treated with oxalyl chloride (0.236 mL, 2.79 mmol), heated at 100° C. for 1 h, cooled to RT, added drop-wise to a solution of N-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)pyrrolidine-1-carboxamide (0.658 g, 2.100 mmol) and pyridine (0.237 mL, 2.94 mmol) in THF (10 mL) and stirred at RT for 2 h. The mixture was concentrated to dryness, treated with satd. NaHCO3, extracted with EtOAc (4×) and the combined organics were dried over Na2SO4 and concentrated to dryness. The residue was treated with MeCN, sonicated and the resulting solid was removed via filtration. The filtrate was concentrated to dryness, suspended in MeCN, sonicated, allowed to stand for 3 h and the resulting solid collected via filtration to afford N-(4-((2-methyl-6-(3-pivaloylureido)pyridin-3-yl)oxy)pyridin-2-yl)pyrrolidine-1-carboxamide (161 mg, 17%). 1H NMR (400 MHz, DMSO-d6): δ 11.16 (s, 1H), 10.41 (s, 1H), 8.70 (s, 1H), 8.09 (d, J=5.7 Hz, 1H), 7.90 (m, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.38-7.37 (m, 1H), 6.55 (dd, J=5.7, 2.4 Hz, 1H), 3.31 (m, 4H), 2.23 (s, 3H), 1.78 (m, 4H), 1.21 (s, 9H); MS (ESI) m/z: 441.2 (M+H+).

Workup

  1. temperaturecooled to RT
  2. concentrationThe mixture was concentrated to dryness
  3. additiontreated with satd
  4. extractionNaHCO3, extracted with EtOAc (4×)
  5. dry with materialthe combined organics were dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. additionThe residue was treated with MeCN
  8. customsonicated
  9. customthe resulting solid was removed via filtration
  10. concentrationThe filtrate was concentrated to dryness
  11. customsonicated
  12. waitto stand for 3 h
  13. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-e3e9e9ccc0d44dc5b68349d2e39a576e
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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