Acetic Acid → HCID 59253057, compound

HRID 884751Notes

Reaction equation

HRID 884751 reaction equation
C(O[C:6](=O)[NH:7][N:8]1[C:17]([CH3:18])=[C:16]([Br:19])[C:15]2[C:10](=[C:11]([F:20])[CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:21])(C)(C)C.[CH:23](=O)C.C([BH3-])#N.[Na+].C(O)(=O)C>FC(F)(F)C(O)=O.[OH-].[K+]>[Br:19][C:16]1[C:15]2[C:10](=[C:11]([F:20])[CH:12]=[CH:13][CH:14]=2)[C:9](=[O:21])[N:8]([NH:7][CH2:6][CH3:23])[C:17]=1[CH3:18]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 59253011HCID 59253011, compound

Product 1

HCID 59253057HCID 59253057, compoundYield 24.8%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 14797Potassium HydroxideSolvent

Procedure

A solution of (4-bromo-8-fluoro-3-methyl-1-oxo-1H-isoquinolin-2-yl)-carbamic acid tert-butyl ester (100.0 mg, 0.2694 mmol) in trifluoroacetic acid (1 mL) was stirred at r.t. for 40 min and evaporated. LC-MS 07-07-2008 12-11-51.wiff:ca 2:1 mixture of the desired intermediate 2-amino-4-bromo-8-fluoro-3-methyl-2H-isoquinolin-1-one [B] (tR=1.01, m/z MH+271.3 & 273.3) and presumably its trifluoroacetyl derivative (tR=1.19, m/z MH+ 367.2 & 369.2). Alternatively, deprotection of BOC group was successfully carried out in conc. HCl solution in methanol under reflux (5 min). It was mixed with 2 ml methanol, 0.3 ml 20% KOH in water, refluxed for 5 min, allowed to cool and quenched with water (3 ml). The precipitate was filtered to 46.2 mg of pale yellow solid as 4:1 mixture of the above compounds. It was suspended in MeOH (3 ml), acetaldehyde (0.20 mL, 3.6 mmol) was added, followed by sodium cyanoborohydride (100.0 mg, 1.591 mmol) and acetic acid (0.4 mL, 7 mmol). It was stirred for 90 min and diluted with 5% aq. KOH (10 ml), allowed to stir for 20 min and filtered to give 20 mg of the title product. LC-MS (m/z) 299.4 & 301.4 (MH30), tR=1.42. 1H NMR (CDCl3, TMS=0 ppm): 1.21 (t, J=7.2 Hz, 3H, Et), 2.77 (overlapping s, 3H, Me), 2.68-3.2 (overlapping very br. d, 2H, Et), 5.89 (t, J=6.8 Hz, 1H, NH), 7.13 (dd, J=8.3, J (HF)=10.9, 1H, C7H), 7.63 (dt, J (d, H—F)=5.05 Hz, J (t)=8.1 Hz, 1H, C6H), 7.74 (d, J=8.3 Hz, 1H, C5H). 13C APT (CDCl3=77.44 ppm): 13.0 (Me of Et), 19.95 (Me), 46.26 (CH2), 99.72 (d, J (C—F)=3.5 Hz, C), 113.78 (d, J (C—F)=21.7 Hz, C7H), 122.24 (d, J (C—F)=4.1 Hz, C5H), 134.03 (d, J (C—F)=10.2 Hz, C6H), 138.02 (C), 142.16 (C3), 158.7 (d, J (C—F)=4.6 Hz, C), 162.56 (d, J (C—F)=264 Hz, C8F). 19F NMR (CFCl3=0 ppm): −110.92 (dd, J=4.5 Hz, J=10.9 Hz).

Workup

  1. customevaporated
  2. additionLC-MS 07-07-2008 12-11-51.wiff:ca 2:1 mixture of the desired intermediate 2-amino-4-bromo-8-fluoro-3-methyl-2H-isoquinolin-1-one [B] (tR=1.01, m/z MH+271.3 & 273.3) and presumably its trifluoroacetyl derivative (tR=1.19, m/z MH+ 367.2 & 369.2)
  3. temperatureunder reflux (5 min)
  4. additionIt was mixed with 2 ml methanol, 0.3 ml 20% KOH in water
  5. temperaturerefluxed for 5 min
  6. temperatureto cool
  7. customquenched with water (3 ml)
  8. filtrationThe precipitate was filtered to 46.2 mg of pale yellow solid as 4:1 mixture of the above compounds
  9. stirringto stir for 20 min
  10. filtrationfiltered

Sources & evidence

ORD record
ord-b11a63dbf3eb42aba68ebbdfb8cbe324
Source dataset
uspto-grants-2012_08
Patent number
US08242134B2

Reaction notes

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