Potassium Carbonate → HCID 86274187, compound

HRID 626563Notes

Reaction equation

HRID 626563 reaction equation
Cl.[CH3:2][N:3]([CH3:8])[CH2:4][C:5](Cl)=[O:6].[NH2:9][C:10]1[CH:15]=[C:14]([O:16][C:17]2[CH:18]=[CH:19][C:20]([NH:23][C:24]([NH:26][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])=[O:25])=[N:21][CH:22]=2)[CH:13]=[CH:12][N:11]=1.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[K+].[K+]>C1COCC1.C(Cl)Cl>[CH3:2][N:3]([CH3:8])[CH2:4][C:5]([NH:9][C:10]1[CH:15]=[C:14]([O:16][C:17]2[CH:18]=[CH:19][C:20]([NH:23][C:24]([NH:26][C:27](=[O:32])[C:28]([CH3:30])([CH3:29])[CH3:31])=[O:25])=[N:21][CH:22]=2)[CH:13]=[CH:12][N:11]=1)=[O:6]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 81531Diisopropylethylamine2×HCID 139949912-(Dimethylamino)acetyl chloride hydrochloride2×HCID 90409811N-((5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

Product 1

HCID 86274187HCID 86274187, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 2-(dimethylamino)acetyl chloride hydrochloride (0.101 g, 0.638 mmol) in THF (5 mL) was added to a 0° C. solution of Example C1 (0.15 g, 0.455 mmol) and DIEA (0.239 mL, 1.366 mmol) in THF (5 mL), allowed to warm to RT and stirred overnight. Additional 2-(dimethylamino)acetyl chloride hydrochloride (0.200 g), DIEA (0.239 mL, 1.366 mmol) and DCM (5 mL) were added and the mixture stirred at RT overnight. The mixture was treated with 10% K2CO3, extracted with DCM (4×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via preparative TLC (MeOH/DCM/TEA) to afford N-((5-((2-(2-(dimethylamino)acetamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (86 mg, 46%). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.95 (s, 1H), 8.26 (d, J=2.9 Hz, 1H), 8.20 (d, J=5.8 Hz, 1H), 8.09 (d, J=9.0 Hz, 1H), 7.75 (dd, J=9.0, 2.9 Hz, 1H), 7.65 (d, J=2.4 Hz, 1H), 6.73 (dd, J=5.8, 2.4 Hz, 1H), 3.07 (s, 2H), 2.25 (s, 6H), 1.21 (s, 9H); MS (ESI) m/z: 415.2 (M+H+).

Workup

  1. stirringthe mixture stirred at RT overnight
  2. extractionextracted with DCM (4×)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified via preparative TLC (MeOH/DCM/TEA)

Sources & evidence

ORD record
ord-04df29429ef240bcb31a2c37279a12b3
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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