Potassium Carbonate → HCID 86274186, compound

HRID 626562

Reaction equation

HRID 626562 reaction equation
[CH2:1]1[CH2:5][N:4]([CH2:6][C:7]([OH:9])=O)[CH2:3][CH2:2]1.S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:20]=[C:19]([O:21][C:22]2[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:36])([CH3:35])[CH3:34])=[O:30])=[N:26][CH:27]=2)[CH:18]=[CH:17][N:16]=1.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C1COCC1>[N:4]1([CH2:6][C:7]([NH:14][C:15]2[CH:20]=[C:19]([O:21][C:22]3[CH:23]=[CH:24][C:25]([NH:28][C:29]([NH:31][C:32](=[O:37])[C:33]([CH3:35])([CH3:34])[CH3:36])=[O:30])=[N:26][CH:27]=3)[CH:18]=[CH:17][N:16]=2)=[O:9])[CH2:3][CH2:2][CH2:1][CH2:5]1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 414564Pyrrolidin-1-ylacetic acidHCID 90409811N-((5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

Product 1

HCID 86274186HCID 86274186, compoundYield 15.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-pyrrolidinylacetic acid (0.082 g, 0.638 mmol) in thionyl chloride (3 mL, 41.1 mmol) and DCM (3 mL) was stirred at RT for 3 h, concentrated to dryness, suspended in THF (5 mL), 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. 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 silica gel chromatography (MeOH/EtOAc). The material was further purified via preparative TLC (MeOH/DCM/TEA) to afford N-((5-((2-(2-(pyrrolidin-1-yl)acetamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (31 mg, 15%). 1H NMR (400 MHz, DMSO-d6): δ 11.23 (s, 1H), 10.44 (s, 1H), 9.98 (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), 7.74 (dd, J=9.0, 2.9 Hz, 1H), 7.64 (d, J=2.4 Hz, 1H), 6.74 (dd, J=5.8, 2.4 Hz, 1H), 3.27 (s, 2H), 2.58 (s, 4H), 1.73-1.71 (m, 4H), 1.21 (s, 9H); MS (ESI) m/z: 441.2 (M+H+).

Workup

  1. concentrationconcentrated to dryness
  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 silica gel chromatography (MeOH/EtOAc)
  7. customThe material was further purified via preparative TLC (MeOH/DCM/TEA)

Sources & evidence

ORD record
ord-d966b9f3bb6f4644a1db04c96882fbfe
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Linked notes

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