4-Methylmorpholine → HCID 45275491, compound

HRID 1667067Notes

Reaction equation

HRID 1667067 reaction equation
[O:1]=[C:2]1[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:5][CH2:4][N:3]1[CH2:19][C:20]([OH:22])=O.C(Cl)(=O)C(Cl)=O.[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([NH2:36])=[N:34][CH:35]=1.CN1CCOCC1>ClCCl>[Cl:29][C:30]1[CH:31]=[CH:32][C:33]([NH:36][C:20](=[O:22])[CH2:19][N:3]2[CH2:4][CH2:5][C:6]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:2]2=[O:1])=[N:34][CH:35]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 661742-Amino-5-chloropyridineHCID 673590132-(2-Oxo-3,3-diphenylpyrrolidin-1-yl)acetic acid

Product 1

HCID 45275491HCID 45275491, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of 2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetic acid (Example 1C, 0.050 g, 0.169 mmol) in dichloromethane (0.5 mL) at room temperature was added a solution of oxalyl chloride in dichloromethane (2.0 M, 0.102 mL, 0.203 mmol). The reaction was stirred for 1 hour and then concentrated under a stream of nitrogen. The resulting acid chloride was dissolved in dichloroethane (0.5 mL), and 5-chloropyridin-2-amine (0.024 g, 0.186 mmol) was added followed by N-methyl morpholine (0.028 mL, 0.254 mmol). The reaction was heated to 70° C. After stirring for 3 hours, the reaction was loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the product was eluted using a gradient of 5% ethyl acetate/hexanes to 75% ethyl acetate/hexanes over 25 minutes (flow=30 mL/minute). The product was contaminated with aminopyridine starting material. A second silica gel column chromatography (SF15-24, Analogix®) eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes over 30 minutes (flow=30 mL/minute) gave the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.44-8.46 (br s, 1H), 8.22 (dd, J=2.5, 0.7 Hz, 1H), 8.09 (d, J=8.8 Hz, 1H), 7.65 (ddd, J=8.8, 2.6, 0.5 Hz, 1H), 7.21-7.39 (m, 10H), 4.19 (s, 2H), 3.54 (t, J=6.5 Hz, 2H), 2.88 (t, J=6.5 Hz, 2H); MS (ESI+) m/z 406 (M+H)+.

Workup

  1. concentrationconcentrated under a stream of nitrogen
  2. dissolutionThe resulting acid chloride was dissolved in dichloroethane (0.5 mL)
  3. stirringAfter stirring for 3 hours
  4. washthe product was eluted
  5. customover 25 minutes
  6. washA second silica gel column chromatography (SF15-24, Analogix®) eluting with a gradient of 5% ethyl acetate/hexanes to 50% ethyl acetate/hexanes over 30 minutes (flow=30 mL/minute)

Sources & evidence

ORD record
ord-adb71e3787e9438c981988dfb4fa2011
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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