Trifluoroacetic acid → (S)-8-((2-amino-4-methylpentyl)oxy)-4-methyl-5H-chromeno[3,4-c]pyridin-5-one

HRID 2369557Notes

Reaction equation

HRID 2369557 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:9][O:10][C:11]1C=C[C:14]2[C:24]3[C:19](=[C:20]([CH3:25])[N:21]=[CH:22][CH:23]=3)[CH2:18][O:17][C:15]=2[CH:16]=1)(C)(C)C.[C:31](O)([C:33](F)(F)F)=[O:32].C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:7][C@@H:8]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]2[C:24]3[C:19](=[C:20]([CH3:25])[N:21]=[CH:22][CH:23]=3)[C:18](=[O:17])[O:32][C:31]=2[CH:33]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86724450HCID 86724450, compound

Product 1

HCID 71726892(S)-8-((2-amino-4-methylpentyl)oxy)-4-methyl-5H-chromeno[3,4-c]pyridin-5-oneYield 10.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-tert-butyl(4-methyl-1-((4-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-yl)carbamate (35 mg, 0.085 mmol) in DCM (3 mL) was cooled to 0° C. and then TFA (0.033 mL, 0.424 mmol) was added. The reaction mixture was stirred at room temperature for 2 h, then neutralized with saturated NaHCO3 and extracted with EtOAc (3×5 mL). Organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to afford crude which was purified by column chromatography on silica gel to afford material which air oxidized during purification to afford (S)-8-((2-amino-4-methylpentyl)oxy)-4-methyl-5H-chromeno[3,4-c]pyridin-5-one (3 mg, 9.19 umol, 10% yield) as yellow solid. 1H NMR (400 MHz, CD3OD) δ 8.67 (d, J=5.6 Hz, 1H) 8.19-8.23 (m, 1H) 8.02-8.06 (d, J=5.6 Hz, 1H) 7.06-7.10 (m, 1H) 6.98 (s, 1H), 4.08-4.14 (m, 1H), 3.91-3.97 (m, 1H), 3.28-3.30 (m, 1H), 3.01 (s, 3H), 1.80-1.88 (m, 1H), 1.41-1.48 (m, 2H), 0.97-1.03 (m, 6H); LCMS (ESI) m/e 327.2 [(M+H)+, calcd for C19H23N2O3 327.2]; LC/MS retention time (Method G): tR=0.82 min; HPLC retention time (method A): tR=8.47 min; HPLC retention time (method B): tR=8.90 min.

Workup

  1. extractionextracted with EtOAc (3×5 mL)
  2. dry with materialOrganic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto afford crude which
  6. customwas purified by column chromatography on silica gel
  7. customto afford material which air
  8. customoxidized during purification

Sources & evidence

ORD record
ord-f15dd9daf94c4143bd3f35ed637d759a
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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