Cyanoacetic acid → N-((5-((2-(2-cyanoacetamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

HRID 626565Notes

Reaction equation

HRID 626565 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.[C:25]([CH2:27][C:28](O)=[O:29])#[N:26].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:25]([CH2:27][C:28]([NH:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:16]([NH:18][C:19](=[O:24])[C:20]([CH3:21])([CH3:23])[CH3:22])=[O:17])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1)=[O:29])#[N:26]

Participants

7

Reactant 5

HCID 9740Cyanoacetic acidHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 90409811N-((5-((2-aminopyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide

Product 1

HCID 86274189N-((5-((2-(2-cyanoacetamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamideYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of Example C1 (0.15 g, 0.455 mmol), cyanoacetic acid (0.080 mL, 1.206 mmol), TBTU (0.258 g, 0.804 mmol) and DIEA (0.35 mL, 2.009 mmol) in DMF (5 mL) was stirred at RT overnight, 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-cyanoacetamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)pivalamide (126 mg, 79%). 1H NMR (400 MHz, DMSO-d6): δ 11.24 (s, 1H), 10.92 (s, 1H), 10.44 (s, 1H), 8.26 (d, J=2.9 Hz, 1H), 8.22 (d, J=5.8 Hz, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.75 (dd, J=9.0, 2.9 Hz, 1H), 7.56 (s, 1H), 6.76 (dd, J=5.7, 2.4 Hz, 1H), 3.93 (s, 2H), 1.21 (s, 9H); MS (ESI) m/z: 397.2 (M+H+).

Workup

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

Sources & evidence

ORD record
ord-c5407631903a4052a7bffb8ef994c7e7
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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