4-Methylmorpholine → HCID 67444981, compound

HRID 1667262Notes

Reaction equation

HRID 1667262 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](O)=[O:15])[C:9]2=[O:17])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[Cl:31][C:32]1[CH:33]=[CH:34][C:35]([NH2:38])=[N:36][CH:37]=1.CN1CCOCC1>CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14]([NH:38][C:35]3[CH:34]=[CH:33][C:32]([Cl:31])=[CH:37][N:36]=3)=[O:15])[C:9]2=[O:17])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 661742-Amino-5-chloropyridineHCID 673571912-(3,3-Bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid

Product 1

HCID 67444981HCID 67444981, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.168 g, 0.506 mmol; Example 58D) was added a catalytic amount of N,N-dimethylformamide followed by oxalyl dichloride (0.404 mL, 0.809 mmol). After stirring for 30 minutes, the reaction was concentrated and dried under high vacuum for 10 minutes. The residue was dissolved in dichloromethane (0.5 mL) and 5-chloropyridin-2-amine (0.052 g, 0.404 mmol) and 4-methylmorpholine (0.089 mL, 0.809 mmol) were added. After 30 minutes, the reaction was loaded onto a GraceResolv™ 40 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 10% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.29 (s, 1H), 8.24-8.20 (m, 1H), 8.09 (d, J=8.8, 1H), 7.65 (dd, J=2.7, 8.8, 1H), 7.36-7.28 (m, 4H), 7.05-6.96 (m, 4H), 4.19 (s, 2H), 3.54 (t, J=6.5, 2H), 2.82 (t, J=6.5, 2H); MS (ESI+) m/z 442.0 (M+H)+.

Workup

  1. concentrationthe reaction was concentrated
  2. customdried under high vacuum for 10 minutes
  3. dissolutionThe residue was dissolved in dichloromethane (0.5 mL)
  4. waitAfter 30 minutes
  5. washthe product eluted with a gradient of 10% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes

Sources & evidence

ORD record
ord-8d27a880bf4e4c1c8a1188da10ffc5dd
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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