HCID 131735120, compound → HCID 86699664, compound

HRID 2207720Notes

Reaction equation

HRID 2207720 reaction equation
Cl.Cl.[NH2:3][CH2:4][C:5]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[C:12]2[C:17]([NH:19][CH3:20])=[O:18])=[CH2:6].[H][H]>CO.[Pd]>[NH2:3][CH2:4][CH:5]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[C:12]2[C:17]([NH:19][CH3:20])=[O:18])[CH3:6]

Participants

5

Reactant 2

HCID 131735120HCID 131735120, compound2×HCID 178418361HCID 178418361, compound2×

Product 1

HCID 86699664HCID 86699664, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

As shown in step 9-viii of Scheme 9, 8-[1-(aminomethyl)vinyl]-N-methyl-quinoline-4-carboxamide, dihydrochloride (compound 2036, 168.8 g, 537 mmol) was stirred in MeOH (1.688 L) and TEA (114.2 g, 157.3 mL, 1.129 mol) was added, followed by the addition of 5% Pd on BaSO4 (22.88 g, 10.75 mmol). The atmosphere of the reaction mixture was replaced with hydrogen gas and the reaction stirred at under 1 atmosphere of hydrogen atmosphere for 16 hours. After this time, the hydrogen atmosphere was removed and the mixture filtered through diatomaceous earth, concentrated under reduced pressure, and treated with 800 mL water and 250 mL DCM. The resulting biphasic mixture was stirred vigorously until most of the solids had dissolved, resulting in a thick mixture that separates on standing. The pH of the aqueous layer was checked and found to be pH=8. This layer was washed with 3×500 mL DCM, the pH adjusted to 14 with 500 mL 6N NaOH, and extracted with an additional 500 mL DCM. The aqueous solution was then treated with 500 g NaCl and it was extracted with an additional 500 mL DCM. The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure to provide 8-(1-aminopropan-2-yl)-N-methylquinoline-4-carboxamide [compound 2037 (racemic mixture) 104.2 g, 80% yield]: LC-MS=244.43 (M+H); 1H NMR (300 MHz, methanol-d4) δ 8.94 (d, J=4.3 Hz, 1H), 8.02 (dd, J=8.3, 1.6 Hz, 1H), 7.72-7.59 (m, 2H), 7.50 (d, J=4.3 Hz, 1H), 4.30 (h, J=7.0 Hz, 1H), 3.04 (dd, J=12.7, 7.0 Hz, 1H), 3.01 (s, 3H), 2.90 (dd, J=12.7, 6.9 Hz, 1H), 1.40 (d, J=7.1 Hz, 3H).

Workup

  1. customAfter this time, the hydrogen atmosphere was removed
  2. filtrationthe mixture filtered through diatomaceous earth
  3. concentrationconcentrated under reduced pressure
  4. additiontreated with 800 mL water and 250 mL DCM
  5. dissolutionhad dissolved
  6. customresulting in a thick mixture that separates on standing
  7. washThis layer was washed with 3×500 mL DCM
  8. extractionextracted with an additional 500 mL DCM
  9. additionThe aqueous solution was then treated with 500 g NaCl and it
  10. extractionwas extracted with an additional 500 mL DCM
  11. dry with materialThe combined organics were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-05ab6f8760344c96a071cc1d4581862e
Source dataset
uspto-grants-2016_06
Patent number
US09376448B2

Reaction notes

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