1-Methylimidazole → HCID 86659290, compound

HRID 2402751Notes

Reaction equation

HRID 2402751 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[N:8]=[C:7]([N:9]2[CH2:13][C@@H:12]3[C@H:14]([OH:17])[CH2:15][CH2:16][C@@H:11]3[CH2:10]2)[CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.CN1C=CN=C1.[Br:33][C:34]1[CH:39]=[CH:38][C:37]([S:40](Cl)(=[O:42])=[O:41])=[CH:36][CH:35]=1>ClCCl>[Br:33][C:34]1[CH:39]=[CH:38][C:37]([S:40]([O:17][C@H:14]2[C@@H:12]3[C@@H:11]([CH2:10][N:9]([C:7]4[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:18])[F:19])[N:8]=4)[CH2:13]3)[CH2:16][CH2:15]2)(=[O:42])=[O:41])=[CH:36][CH:35]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 7396p-Bromobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 54674495HCID 54674495, compound

Product 1

HCID 86659290HCID 86659290, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (3aR,4R,6aS)-2-[6-(trifluoromethyl)pyridin-2-yl]octahydrocyclopenta[c]pyrrol-4-ol (3.2 g, 11.75 mmol) from Example 30 in dichloromethane (15 mL) was added triethylamine (4.10 mL, 29.4 mmol) followed by 1-methylimidazole (0.281 mL, 3.53 mmol). The solution was cooled to 0° C. and 4-bromobenzene-1-sulfonyl chloride (4.50 g, 17.63 mmol) was added. The solution was warmed to room temperature (solution turned cloudy) and stirred for 16 hours. The reaction mixture was diluted with dichloromethane (12 mL) and washed with aqueous hydrogen chloride (0.1 N, 2×10 mL) and water (10 mL). The organic phase was dried over sodium sulfate and concentrated. The crude material was purified by silica gel chromatography using 0-60% dichloromethane/hexane as eluent to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 7.99-7.90 (m, 2H), 7.77-7.67 (m, 2H), 7.51 (t, J=7.9, 1H), 6.99 (d, J=7.3, 1H), 6.45 (d, J=8.6, 1H), 5.17 (q, J=6.1, 1H), 3.69 (dd, J=11.4, 4.6, 1H), 3.57-3.47 (m, 1H), 3.37 (dd, J=11.4, 8.9, 1H), 3.23 (dd, J=10.7, 4.5, 1H), 2.90-2.78 (m, 1H), 2.67-2.54 (m, 1H), 2.02-1.88 (m, 1H), 1.80 (dq, J=8.2, 6.0, 1H), 1.70 (dtd, J=13.5, 8.6, 7.0, 1H), 1.51-1.37 (m, 1H); MS (ESI+) m/z 491 (M+H)+.

Workup

  1. temperatureThe solution was warmed to room temperature (solution turned cloudy)
  2. washwashed with aqueous hydrogen chloride (0.1 N, 2×10 mL) and water (10 mL)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-f6c67b56ce5041d29db694791584153a
Source dataset
uspto-grants-2014_08
Patent number
US08796470B2

Reaction notes

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