Hydrochloric Acid → HCID 66996571, compound

HRID 2363631Notes

Reaction equation

HRID 2363631 reaction equation
[F:1][C@H:2]1[CH2:6][N:5](C(OC(C)(C)C)=O)[C@H:4]([C:14](=[O:34])[NH:15][C@@H:16]2[C@@H:23]3[C@@H:19]([CH2:20][N:21]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=4)[CH2:22]3)[CH2:18][CH2:17]2)[CH2:3]1.Cl.O1CCOCC1>>[F:1][C@@H:2]1[CH2:6][NH:5][C@H:4]([C:14]([NH:15][C@@H:16]2[C@@H:23]3[C@@H:19]([CH2:20][N:21]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=4)[CH2:22]3)[CH2:18][CH2:17]2)=[O:34])[CH2:3]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66997629HCID 66997629, compound

Product 1

HCID 66996571HCID 66996571, compound

Procedure

In a 4 mL vial was added (2S,4R)-tert-butyl 4-fluoro-2-((3aR,4S,6aS)-2-(3-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrol-4-ylcarbamoyl)pyrrolidine-1-carboxylate from Step 3 (63 mg, 0.130 mmol) and 4 N HCl in 1,4-dioxane (0.487 mL, 1.948 mmol) to give a colorless solution. The reaction was stirred at room temperature overnight, and the solvent was then removed in vacuo. The residue was purified using a 12 g silica gel cartridge eluted with a gradient of 0-2.5% methanol (2 N ammonia)/dichloromethane over 20 minutes to give (4S)-4-fluoro-N-{(3aR,4S,6aS)-2-[3-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-4-yl}-L-prolinamide: 1H NMR (500 MHz, pyridine-d5) δ ppm 8.31 (d, J=7.5, 1H), 7.33 (dd, J=10.1, 5.7, 1H), 7.06 (d, J=7.6, 1H), 6.90 (s, 1H), 6.75 (dd, J=8.3, 2.1, 1H), 5.30-5.12 (m, 1H), 4.30 (dt, J=14.4, 7.3, 2H), 3.72-3.55 (bs, 1H), 3.50-3.43 (m, 1H), 3.32 (ddd, J=21.0, 13.1, 0.8, 1H), 3.23 (dd, J=9.9, 8.0, 1H), 3.13 (dd, J=9.5, 8.2, 1H), 2.99 (dd, J=9.7, 4.1, 1H), 2.96-2.84 (m, 1H), 2.76-2.67 (m, 1H), 2.66-2.52 (m, 2H), 2.26 (dddd, J=39.3, 14.8, 7.9, 4.3, 1H), 2.07 (td, J=12.3, 6.8, 1H), 1.93 (dtd, J=13.1, 7.9, 5.2, 1H), 1.60 (ddd, J=16.0, 12.6, 7.8, 1H), 1.38 (ddd, J=13.2, 7.7, 6.7, 1H); MS (ESI+) m/z 386 (M+H)+.

Workup

  1. customto give a colorless solution
  2. customthe solvent was then removed in vacuo
  3. customThe residue was purified
  4. washeluted with a gradient of 0-2.5% methanol (2 N ammonia)/dichloromethane over 20 minutes

Sources & evidence

ORD record
ord-6094043c8ebb46fa8d2f8680068515aa
Source dataset
uspto-grants-2014_04
Patent number
US08691865B2

Reaction notes

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