Trimethylacetamide → HCID 90403362, compound

HRID 1049361Notes

Reaction equation

HRID 1049361 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]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]([C:28]3[CH:29]=[N:30][C:31]([N:34]([CH3:42])[C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:32][CH:33]=3)[CH:23]=2)=[CH:17][CH:16]=1>ClCCCl.C(Cl)Cl.[Cl-].[Na+].O>[CH3:42][N:34]([C:31]1[N:30]=[CH:29][C:28]([C:24]2[CH:23]=[C:22]([O:21][C:18]3[CH:19]=[N:20][C:15]([NH:14][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])=[CH:16][CH:17]=3)[CH:27]=[CH:26][N:25]=2)=[CH:33][CH:32]=1)[C:35](=[O:41])[O:36][C:37]([CH3:38])([CH3:39])[CH3:40]

Participants

7

Reactant 3

HCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 131736005HCID 131736005, compound

Product 1

HCID 90403362HCID 90403362, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 2,2,2-trimethylacetamide (0.062 g, 0.610 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.080 mL, 0.915 mmol), stirred at RT for 1 h, then heated at 75° C. for 3 h. The mixture was cooled to RT, treated with a solution of tert-butyl (4-((6-aminopyridin-3-yl)oxy)-[2,3′-bipyridin]-6′-yl)(methyl)carbamate (0.12 g, 0.305 mmol) and TEA (0.170 mL, 1.220 mmol) in DCM (3 mL) and stirred at RT for 2 h. The mixture was treated with brine, extracted with DCM (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex) to afford tert-butyl methyl(4-((6-(3-pivaloylureido)pyridin-3-yl)oxy)-[2,3′-bipyridin]-6′-yl)carbamate (100 mg, 63%) as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.02 (d, J=2.5 Hz, 1H), 8.55 (d, J=5.7 Hz, 1H), 8.37 (dd, J=8.8, 2.5 Hz, 1H), 8.30 (d, J=2.9 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.77-7.76 (m, 2H), 7.65 (d, J=2.4 Hz, 1H), 6.89 (dd, J=5.7, 2.4 Hz, 1H), 3.33 (s, 3H), 1.47 (s, 9H), 1.21 (s, 9H); MS (ESI) m/z: 521.3 (M+H+).

Workup

  1. temperatureheated at 75° C. for 3 h
  2. temperatureThe mixture was cooled to RT
  3. stirringstirred at RT for 2 h
  4. extractionextracted with DCM (2×)
  5. washthe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record
ord-0fcda5da80204678bbaf37a13ecb67d8
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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