Diisopropylethylamine → 3,3-bis(4-fluorophenyl)-1-(2-oxo-2-((4aS,7aS)-tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl)ethyl)pyrrolidin-2-one

HRID 1667246Notes

Reaction equation

HRID 1667246 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14]([OH:16])=O)[C:9]2=[O:17])=[CH:4][CH:3]=1.[N:25]1(C(OC(C)(C)C)=O)[CH2:30][CH2:29][CH2:28][C@H:27]2[CH2:31][NH:32][CH2:33][C@@H:26]12.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:8]2([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14](=[O:16])[N:32]3[CH2:31][C@H:27]4[C@H:26]([NH:25][CH2:30][CH2:29][CH2:28]4)[CH2:33]3)[C:9]2=[O:17])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1519435(4aS,7aS)-tert-Butyl octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 674471943,3-bis(4-fluorophenyl)-1-(2-oxo-2-((4aS,7aS)-tetrahydro-1H-pyrrolo[3,4-b]pyridin-6(2H,7H,7aH)-yl)ethyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (Example 58D) (0.331 g, 1 mmol) and (4aS,7aS)-tert-butyl octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylate (Example 50B) (0.226 g, 1 mmol) in methylene chloride (20 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.38 g, 1 mmol) and diisopropylethylamine (0.45 mL). The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with methylene chloride, and then washed with 1 N HCl, water, 1 N NaOH, and water. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The obtained residue was purified by silica gel chromatography eluting with ethyl acetate to yield the t-butoxycarbonyl-protected title compound. That material was dissolved in dichloromethane (10 mL) and treated with trifluoroacetic acid (2 mL) for 1 hour at room temperature. The reaction mixture was concentrated and partitioned between saturated aqueous NaHCO3 solution and dichloromethane. The organic layer was separated, dried over MgSO4 and concentrated to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.35 (m, 4H), 7.00 (m, 4H), 4.25 (dd, 1H), 3.96 (t, J=16.78 Hz, 1H), 3.47 (m, 7H), 3.00 (m, 1H), 2.78 (m, 2H), 2.63 (m, 1H), 2.27 (m, 1H), 1.72 (m, 2H) 1.45 (m, 2H); MS (ESI+) m/z 440 (M+H)+.

Workup

  1. washwashed with 1 N HCl, water, 1 N NaOH, and water
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe obtained residue was purified by silica gel chromatography
  5. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-c2d6ef75c84c45a6852cde810360159a
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

Loading…