HCID 68503636, compound → HCID 59463923, compound

HRID 1713477Notes

Reaction equation

HRID 1713477 reaction equation
[Si]([O:18][CH2:19][CH2:20][C:21]1([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[N:25]([C:26]2[S:27][C:28]3[CH2:29][N:30]([CH3:35])[CH2:31][CH2:32][C:33]=3[N:34]=2)[N:24]=[C:23]([C:36]2[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=2[F:43])[S:22]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C(#N)C>[F:43][C:37]1[CH:38]=[CH:39][C:40]([F:42])=[CH:41][C:36]=1[C:23]1[S:22][C:21]([CH2:20][CH2:19][OH:18])([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[N:25]([C:26]2[S:27][C:28]3[CH2:29][N:30]([CH3:35])[CH2:31][CH2:32][C:33]=3[N:34]=2)[N:24]=1

Participants

3

Reactant 1

HCID 68503636HCID 68503636, compound

Product 1

HCID 59463923HCID 59463923, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(2-(2-(tert-butyldiphenylsilyloxy)ethyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (0.070 g, 0.098 mmol) in 2 mL of anhydrous acetonitrile was added HF-TEA (0.160 mL, 0.99 mmol). The solution was stirred at room temperature for 16 hours then slowly quenched with saturated NaHCO3 (20 mL). The mixture was extracted with EtOAc (3×10 mL) and the combined organic phases were washed with brine (10 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (0-1% MeOH/DCM) and the residue was dissolved in 2 mL of methanol and treated with 1N HCl/MeOH (2 mL). After stirring for 10 minutes, the solution was concentrated in vacuo. The residue was triturated with diethyl ether, filtered, washed with ether and dried in vacuo to afford the desired product as a yellow powder, 0.023 g, 42%. MS ESI (+) m/z 473 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 7.59 (m, 1H), 7.44 (d, 2H, J=7.5 Hz), 7.32 (m, 2H), 7.26 (m, 1H), 7.07 (m, 2H), 4.10 (m, 1H), 3.96 (m, 1H), 3.65 (m, 1H), 3.54 (q, 2H, J=30.2, 14.3 Hz), 2.83 (m, 1H), 2.72 (m, 2H), 2.57 (m, 2H), 2.48 (s, 3H) ppm.

Workup

  1. customthen slowly quenched with saturated NaHCO3 (20 mL)
  2. extractionThe mixture was extracted with EtOAc (3×10 mL)
  3. washthe combined organic phases were washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography (0-1% MeOH/DCM)
  7. dissolutionthe residue was dissolved in 2 mL of methanol
  8. additiontreated with 1N HCl/MeOH (2 mL)
  9. stirringAfter stirring for 10 minutes
  10. concentrationthe solution was concentrated in vacuo
  11. customThe residue was triturated with diethyl ether
  12. filtrationfiltered
  13. washwashed with ether
  14. customdried in vacuo

Sources & evidence

ORD record
ord-77b00f374fa24e8888782869d1f80a09
Source dataset
uspto-grants-2010_09
Patent number
US07795282B2

Reaction notes

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