Thiophenol → HCID 136341338, compound

HRID 579313Notes

Reaction equation

HRID 579313 reaction equation
C[O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:5][C:4]=1[C:15]1[S:19][C:18]([N:20]([CH3:31])[CH:21]2[CH2:26][C:25]([CH3:28])([CH3:27])[NH:24][C:23]([CH3:30])([CH3:29])[CH2:22]2)=[N:17][N:16]=1.C([O-])([O-])=O.[Na+].[Na+].C1(S)C=CC=CC=1>CN1C(=O)CCC1>[CH3:31][N:20]([CH:21]1[CH2:26][C:25]([CH3:28])([CH3:27])[NH:24][C:23]([CH3:30])([CH3:29])[CH2:22]1)[C:18]1[S:19][C:15]([C:4]2[CH:5]=[CH:6][C:7]([C:9]3[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=3)=[CH:8][C:3]=2[OH:2])=[N:16][N:17]=1

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 10340Sodium CarbonateHCID 86727133HCID 86727133, compound

Product 1

HCID 136341338HCID 136341338, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
190 °C

Procedure

To a stirred solution of 5-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (129 mg, 0.293 mmol) in NMP (3 mL) was added Na2CO3 (47 mg, 0.439 mmol) followed by PhSH (35 μL, 0.337 mmol). The resulting mixture was sealed, evacuated and back filled with nitrogen (×3), then heated at 190° C. for 20 minutes under microwave irradiation. The reaction mixture was diluted with MeOH (10 mL) and filtered through celite. The filtrate was acidified by addition of acetic acid (3 mL) and loaded onto a 2 g SCX cartridge (pre-wet with MeOH). The cartridge was washed with MeOH (15 mL) and flushed with 7M NH3 in MeOH (15 mL). The MeOH/NH3 was removed in vacuo to afford the crude product as a brown solid. The crude material was purified by UV-directed preparative HPLC under basic (5 mM NH4OH) conditions, collecting at 352 nm, to afford the title compound as a pale brown glass-like solid (0.096 g, 77% yield). LC-MS: Rt 0.88 min; MS m/z 427.2 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.13 (s, 1H), 7.86-7.78 (m, 2H), 7.17-7.10 (m, 2H), 4.35-4.25 (m, 1H), 3.87 (s, 3H), 2.99 (s, 3H), 1.62 (dd, J=11.87, 3.28 Hz, 2H), 1.43 (t, J=12.13 Hz, 2H), 1.21 (s, 6H), 1.09 (s, 6H). LC-MS: Rt 1.69 min; MS m/z 427.4 [M+H]+ [Method B]. HR-MS: Rt 1.49 mins; MS m/z 427.2660 [M+H]+ [Method C].

Workup

  1. customThe resulting mixture was sealed
  2. customevacuated
  3. additionback filled with nitrogen (×3)
  4. additionThe reaction mixture was diluted with MeOH (10 mL)
  5. filtrationfiltered through celite
  6. additionThe filtrate was acidified by addition of acetic acid (3 mL)
  7. washThe cartridge was washed with MeOH (15 mL)
  8. customflushed with 7M NH3 in MeOH (15 mL)
  9. customThe MeOH/NH3 was removed in vacuo
  10. customto afford the crude product as a brown solid
  11. customThe crude material was purified by UV-directed preparative HPLC under basic (5 mM NH4OH) conditions
  12. customcollecting at 352 nm

Sources & evidence

ORD record
ord-4a21267688a74984936cd0e3d8ee9d90
Source dataset
uspto-grants-2015_05
Patent number
US09040712B2

Reaction notes

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