Trimethylacetamide → HCID 90403157, compound

HRID 1049365Notes

Reaction equation

HRID 1049365 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[O:4].C(Cl)(=O)[C:9](Cl)=[O:10].[C:14]([O:18][C:19]([N:21]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[C:22]1[N:27]=[CH:26][C:25]([C:28]2[CH:33]=[C:32]([O:34][C:35]3[CH:36]=[N:37][C:38]([NH2:41])=[CH:39][CH:40]=3)[CH:31]=[CH:30][N:29]=2)=[CH:24][CH:23]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>ClCCCl.C(Cl)Cl.[Cl-].[Na+].O>[C:45]([O:44][C:42]([N:21]([C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])[C:22]1[N:27]=[CH:26][C:25]([C:28]2[CH:33]=[C:32]([O:34][C:35]3[CH:40]=[CH:39][C:38]([NH:41][C:9]([NH:5][C:3](=[O:4])[C:2]([CH3:7])([CH3:6])[CH3:1])=[O:10])=[N:37][CH:36]=3)[CH:31]=[CH:30][N:29]=2)=[CH:24][CH:23]=1)=[O:43])([CH3:48])([CH3:47])[CH3:46]

Participants

7

Reactant 3

HCID 12957TrimethylacetamideHCID 65578Oxalyl chlorideHCID 90426427HCID 90426427, compound

Product 1

HCID 90403157HCID 90403157, compoundYield 91%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 2,2,2-trimethylacetamide (0.084 g, 0.834 mmol) in DCE (3 mL) was treated with oxalyl chloride (0.073 mL, 0.834 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 6′-(bis(tert-butoxycarbonyl)amino)-4-((6-aminopyridin-3-yl)oxy)-[2,3′-bipyridine](0.2 g, 0.417 mmol) and TEA (0.174 mL, 1.251 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 and concentrated to dryness to afford N-((5-((6′-(bis(tert-butoxycarbonyl)amino)-[2,3′-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (230 mg, 91%) as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1H), 10.45 (br s, 1H), 9.08 (d, J=2.5 Hz, 1H), 8.58 (d, J=5.7 Hz, 1H), 8.49 (dd, J=8.5, 2.5 Hz, 1H), 8.30 (d, J=2.9 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.78 (dd, J=9.0, 2.9 Hz, 1H), 7.73 (d, J=2.4 Hz, 1H), 7.48 (d, J=8.4 Hz, 1H), 6.94 (dd, J=5.7, 2.4 Hz, 1H), 1.40 (s, 18H), 1.21 (s, 9H); MS (ESI) m/z: 607.3 (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

Sources & evidence

ORD record
ord-c06ae3388762438da28514abb2863ba0
Source dataset
uspto-grants-2016_07
Patent number
US09382228B2

Reaction notes

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