Triethylamine → HCID 66997611, compound

HRID 2363638Notes

Reaction equation

HRID 2363638 reaction equation
[F:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14](=[O:24])[NH:15][C@@H:16]2[C@@H:23]3[C@@H:19]([CH2:20][NH:21][CH2:22]3)[CH2:18][CH2:17]2)[CH2:3]1.Br[C:26]1[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=1.C(N(CC)CC)C.O.C(O)C>C(O)C>[F:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:12])([CH3:13])[CH3:11])=[O:8])[C@H:4]([C:14](=[O:24])[NH:15][C@@H:16]2[C@@H:23]3[C@@H:19]([CH2:20][N:21]([C:26]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=4)[CH2:22]3)[CH2:18][CH2:17]2)[CH2:3]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27815432-Bromo-4-(trifluoromethyl)pyridineHCID 19096565Water ethanolHCID 66997026HCID 66997026, compound

Product 1

HCID 66997611HCID 66997611, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
82 °C

Procedure

In a 4 mL vial were combined (2S,4R)-tert-butyl 4-fluoro-2-((3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)pyrrolidine-1-carboxylate from Example 617 Step 2 (80 mg, 0.234 mmol), 2-bromo-4-(trifluoromethyl)pyridine (74.1 mg, 0.328 mmol), and triethylamine (0.131 mL, 0.937 mmol) in ethanol (0.1 mL). The reaction was heated at 82° C. for 1 day. To the reaction mixture was added 90% water/ethanol (1 mL), and then the liquid layer was decanted. This crude material was purified using a 12 g silica gel cartridge eluted with a gradient of 0-60% acetone/hexane over 20 minutes to give (2S,4R)-tert-butyl 4-fluoro-2-((3aR,4S,6aS)-2-(4-(trifluoromethyl)pyridin-2-yl)octahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)pyrrolidine-1-carboxylate: 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 8.34 (d, J=5.2, 1H), 7.93 (bs, 1H), 6.73 (d, J=5.1, 1H), 6.60 (s, 1H), 5.33-5.10 (m, 1H), 4.62 (t, J=7.9, 1H), 4.34-4.22 (m, 1H), 3.96 (dd, J=21.9, 13.0, 1H), 3.66 (tdd, J=16.6, 12.2, 5.7, 3H), 3.57-3.50 (m, 1H), 3.30 (dd, J=10.9, 4.3, 1H), 2.76 (tdd, J=13.1, 8.5, 4.5, 2H), 2.54-2.35 (m, 2H), 2.16 (dd, J=12.5, 5.8, 1H), 2.04-1.91 (m, 1H), 1.72 (ddd, J=15.3, 12.9, 7.8, 1H), 1.51 (s, 9H), 1.44 (dd, J=9.2, 4.0, 1H); MS (ESI+) m/z 487 (M+H)+.

Workup

  1. customthe liquid layer was decanted
  2. customThis crude material was purified
  3. washeluted with a gradient of 0-60% acetone/hexane over 20 minutes

Sources & evidence

ORD record
ord-b331a9c6bc7d4596b692bde12dfce53d
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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