Acetic Acid → HCID 25205682, compound

HRID 423929Notes

Reaction equation

HRID 423929 reaction equation
N[C:2]1[CH:3]=[C:4]([NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]([CH3:11])([CH3:10])[CH3:9].[C:26](O)(=O)C.C=O.[C:32]([BH3-])#[N:33].[Na+]>C(Cl)Cl.CO.CCOCC>[CH3:26][N:33]([CH3:32])[C:2]1[CH:3]=[C:4]([NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[C:8]([CH3:11])([CH3:10])[CH3:9]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 712Formaldehyde2×HCID 5003444Sodium cyanoborohydrideHCID 57567354N-(3-amino-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide

Product 1

HCID 25205682HCID 25205682, compoundYield 17%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-(3-amino-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (271) (600 mg, 1.8 mmol) in CH2Cl2 (15 mL) and methanol (5 mL) were added acetic acid (250 μL) and formaldehyde (268 μL, 3.6 mmol, 37 wt % in water). After 10 min, sodium cyanoborohydride (407 mg, 6.5 mmol) was added in one portion. Additional formaldehyde (135 μL, 1.8 mmol, 37 wt % in water) was added at 1.5 and 4.2 h. After 4.7 h, the mixture was diluted with ether (40 mL), washed with water (25 mL) and brine (25 mL), dried (Na2SO4), filtered, and concentrated. The resulting red-brown foam was purified by preparative HPLC to afford N-(3-dimethylamino-4-tert-butyl-phenyl)-4-oxo-1H-quinoline-3-carboxamide (485) (108 mg, 17%). 1H NMR (300 MHz, CDCl3) δ□13.13 (br s, 1H), 12.78 (s, 1H), 8.91 (br s, 1H), 8.42 (br s, 1H), 8.37 (d, J=8.1 Hz, 1H), 7.72-7.58 (m, 2H), 7.47-7.31 (m, 3H), 3.34 (s, 6H), 1.46 (s, 9H); HPLC ret. time 2.15 min, 10-100% CH3CN, 5 min run; ESI-MS 364.3 m/z (MH+).

Workup

  1. waitAfter 4.7 h
  2. washwashed with water (25 mL) and brine (25 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting red-brown foam was purified by preparative HPLC

Sources & evidence

ORD record
ord-71c3c27b07204a0daa8cf671f598825d
Source dataset
uspto-grants-2012_01
Patent number
US08101767B2

Reaction notes

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