N,2,2,6,6-Pentamethylpiperidin-4-amine → HCID 86727157, compound

HRID 579336Notes

Reaction equation

HRID 579336 reaction equation
Br[C:2]1[S:3][C:4]([C:7]2[C:12]([O:13][CH3:14])=[CH:11][CH:10]=[CH:9][C:8]=2[F:15])=[N:5][N:6]=1.[CH3:16][NH:17][CH:18]1[CH2:23][C:22]([CH3:25])([CH3:24])[NH:21][C:20]([CH3:27])([CH3:26])[CH2:19]1>CN1C(=O)CCC1.C([O-])(O)=O.[Na+].O>[F:15][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([O:13][CH3:14])[C:7]=1[C:4]1[S:3][C:2]([N:17]([CH3:16])[CH:18]2[CH2:19][C:20]([CH3:26])([CH3:27])[NH:21][C:22]([CH3:25])([CH3:24])[CH2:23]2)=[N:6][N:5]=1

Participants

6

Reactant 2

HCID 13657792N,2,2,6,6-Pentamethylpiperidin-4-amineHCID 654333082-Bromo-5-(2-fluoro-6-methoxyphenyl)-1,3,4-thiadiazole

Product 1

HCID 86727157HCID 86727157, compoundYield 28%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A stirred solution of 2-bromo-5-(2-fluoro-6-methoxyphenyl)-1,3,4-thiadiazole (335 mg, 1.159 mmol) and N,2,2,6,6-pentamethylpiperidin-4-amine (197 mg, 1.159 mmol) in NMP (2.5 mL) was heated at 120° C. for ˜18 hours. The reaction mixture was diluted with saturated NaHCO3(aq) (30 mL), water (20 mL), and extracted with DCM (75 mL). The organic phase was separated, dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to afford the crude product as a brown oil/liquid. The crude material was purified by UV directed preparative HPLC under acidic conditions (0.1% TFA), collecting at 298 nm. The product containing fractions were combined and loaded onto a 5 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (30 mL) then flushed with 7M NH3 in MeOH (20 mL). The MeOH/NH3 was removed in vacuo to afford the title compound as an orange oil (121 mg, 28% yield). LC-MS: Rt 0.88 min; MS m/z 379.4 [M+H]+; [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.49 (td, J=8.34, 6.57 Hz, 1H), 7.03 (d, J=8.59 Hz, 1H), 6.97 (t, J=9.09 Hz, 1H), 4.26-4.36 (m, 1H), 3.86 (s, 3H), 2.98 (s, 3H), 1.62 (dd, J=11.62, 2.53 Hz, 2H), 1.42 (t, J=12.13 Hz, 2H), 1.27 (br. s., 1H), 1.20 (s, 6H), 1.09 (s, 6H).

Workup

  1. extractionextracted with DCM (75 mL)
  2. customThe organic phase was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customto afford the crude product as a brown oil/liquid
  7. customThe crude material was purified by UV
  8. customcollecting at 298 nm
  9. additionThe product containing fractions
  10. washThe cartridge was washed with MeOH (30 mL)
  11. customthen flushed with 7M NH3 in MeOH (20 mL)
  12. customThe MeOH/NH3 was removed in vacuo

Sources & evidence

ORD record
ord-51fcacf28e6d4214ab607833fd52df46
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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