Boron tribromide → 2-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenol

HRID 579352Notes

Reaction equation

HRID 579352 reaction equation
C[O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:6]=[CH:5][C:4]=1[C:14]1[S:18][C:17]([N:19]([CH3:30])[CH:20]2[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)=[N:16][N:15]=1.B(Br)(Br)Br>C(Cl)Cl>[CH3:30][N:19]([CH:20]1[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]1)[C:17]1[S:18][C:14]([C:4]2[CH:5]=[CH:6][C:7]([N:9]3[CH:13]=[CH:12][CH:11]=[N:10]3)=[CH:8][C:3]=2[OH:2])=[N:15][N:16]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 867271305-(2-Methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 1363413452-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)-5-(1H-pyrazol-1-yl)phenolYield 51.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (Example 1) (30 mg, 0.070 mmol) in DCM (1.5 mL) was added BBr3 (1M solution in heptane, 0.352 mL, 0.352 mmol). The resulting bright yellow suspension was stirred at room temperature for 2 h. The reaction mixture was quenched by addition of MeOH (5 mL) and the resulting solution was loaded onto a 1 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (10 mL) then flushed with 7M NH3 in MeOH (15 mL). The solvent was evaporated in vacuo. The resulting crude material was sonicated in MeOH (2 mL) and the resulting suspension was filtered under vacuum to afford the title compound as a pale yellow solid (14.9 mg, 51.4% yield). LC-MS: Rt 0.55 min; MS m/z 413.3 [M+H]+ [Method D]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47 (d, J=2.02 Hz, 1H), 7.99 (d, J=8.59 Hz, 1H), 7.73-7.78 (m, 1H), 7.47 (d, J=1.52 Hz, 1H), 7.36 (d, J=8.59 Hz, 1H), 6.53-6.58 (m, 1H), 4.33 (t, J=12.13 Hz, 1H), 2.99 (s, 3H), 1.58-1.69 (m, 2H), 1.47 (t, J=12.13 Hz, 2H), 1.23 (s, 6H), 1.12 (s, 6H).

Workup

  1. customThe reaction mixture was quenched by addition of MeOH (5 mL)
  2. washThe cartridge was washed with MeOH (10 mL)
  3. customthen flushed with 7M NH3 in MeOH (15 mL)
  4. customThe solvent was evaporated in vacuo
  5. customThe resulting crude material was sonicated in MeOH (2 mL)
  6. filtrationthe resulting suspension was filtered under vacuum

Sources & evidence

ORD record
ord-df5778d4ef3a41c5a5a46ed6698b6463
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

Loading…