Triethylamine → HCID 46213877, compound

HRID 2363592Notes

Reaction equation

HRID 2363592 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[S:12]([N:15]1[CH2:19][C@@H:18]2[C@@H:20]([NH2:23])[CH2:21][CH2:22][C@@H:17]2[CH2:16]1)(=[O:14])=[O:13].Br[C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=1.C(N(CC)CC)C>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:5]=[CH:4][C:3]=1[S:12]([N:15]1[CH2:19][C@@H:18]2[C@@H:20]([NH:23][C:25]3[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][N:26]=3)[CH2:21][CH2:22][C@@H:17]2[CH2:16]1)(=[O:13])=[O:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 66590102HCID 66590102, compound

Product 1

HCID 46213877HCID 46213877, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
86 °C

Procedure

(3aR,4S,6aS)-2-{[2-Chloro-4-(trifluoromethyl)phenyl]sulfonyl}octahydrocyclopenta[c]pyrrol-4-amine (70 mg, 0.190 mmol) from Step B of Example 284, 2-bromo-5-(trifluoromethyl)pyridine (42.9 mg, 0.190 mmol), and triethylamine (0.079 mL, 0.569 mmol) were combined in ethanol (0.6 mL). The reaction was heated at 86° C. for 5 days and the solvent was evaporated in vacuo. The resultant material was purified using a 12 g silica gel cartridge with a gradient of 0-0.8% methanol (2 N ammonia)/dichloromethane over 20 minutes to give crude product. It was further purified by loading it onto 2×0.25 mm preparative thin-layer chromatography plate and eluted with 30% acetone/hexanes to give the title compound: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.50-8.52 (bs, 1H), 8.40 (d, J=8.2 Hz, 1H), 8.03 (s, 1H), 7.96-7.98 (m, 1H), 7.75-7.78 (m, 1H), 7.54-7.59 (m, 1H), 6.59 (d, J=8.8 Hz, 1H), 4.30-4.42 (m, 1H), 3.89 (dd, J=10.2, 2.7 Hz, 1H), 3.57 (dd, J=10.2, 7.0 Hz, 1H), 3.43 (dd, J=9.9, 6.7 Hz, 1H), 3.39 (dd, J=10.0, 2.9 Hz, 1H), 2.68 (d, J=3.5 Hz, 2H), 2.13-2.20 (m, 1H), 1.90-1.97 (m, 1H), 1.59-1.66 (m, 1H), 1.40-1.48 (m, 1H); MS (ESI+) m/z 514 (M+H)+.

Workup

  1. customthe solvent was evaporated in vacuo
  2. customThe resultant material was purified
  3. customover 20 minutes
  4. customto give crude product
  5. customIt was further purified
  6. washeluted with 30% acetone/hexanes

Sources & evidence

ORD record
ord-bd893bea8a5f408f87273e8bf37eca3c
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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