Dimethylformamide → HCID 58081201, compound

HRID 928429Notes

Reaction equation

HRID 928429 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([CH2:15][NH2:16])=[C:10]([CH3:17])[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[C:19](O)(=[O:22])[C:20]#[CH:21].CCN(C(C)C)C(C)C.CCCP(=O)=O.CN(C=O)C>C(Cl)Cl>[CH3:14][C:12]1[C:11]([CH2:15][NH:16][C:19](=[O:22])[C:20]#[CH:21])=[C:10]([CH3:17])[N:9]=[C:8]([NH:7][C:6](=[O:18])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH:13]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 10110Propiolic AcidHCID 81531DiisopropylethylamineHCID 16167369Propylphosphoric anhydrideHCID 22475372N-[5-(aminomethyl)-4,6-dimethyl(2-pyridyl)] (tert-butoxy)carboxamide

Product 1

HCID 58081201HCID 58081201, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of (5-aminomethyl-4,6-dimethyl-pyridin-2-yl)-carbamic acid tert-butyl ester (4.50 g, 17.90 mmol), propiolic acid (0.918 ml, 14.92 mmol), DIPEA (7.82 ml, 44.8 mmol) in DCM (140 ml) at 23° C. was added dropwise over 5 min 50% propylphosphonic anhydride in DMF (12.5 ml, 21.41 mmol). The reaction was stirred at 23° C. for 1 day. The reaction was quenched by addition of brine, and the phases were separated. The aqueous phase was further extracted with DCM, and the combined organic phase was dried over Na2SO4, filtered, and evaporated to provide the crude product, which was purified by flash column chromatography (silica gel 0.040-0.063 mm, 160 g, flow rate 60 ml/min, detection at 220 nm, MeOH in DCM 0->1% over 10 min, then 1->5% over 20 min) to yield the title compound. HPLC (Method G) Rt=1.333 min; MS (Method F) [M+H]+=304.31.

Workup

  1. customThe reaction was quenched by addition of brine
  2. customthe phases were separated
  3. extractionThe aqueous phase was further extracted with DCM
  4. dry with materialthe combined organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto provide the crude product, which
  8. customwas purified by flash column chromatography (silica gel 0.040-0.063 mm, 160 g, flow rate 60 ml/min, detection at 220 nm, MeOH in DCM 0->1% over 10 min

Sources & evidence

ORD record
ord-08d229b75b064a92ac2961c72e86e62b
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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