1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-3-(6-(pyrrolidine-1-carbonyl)pyridin-3-yloxy)pyrrolidin-2-one

HRID 407994Notes

Reaction equation

HRID 407994 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([F:31])[C:6]([N:9]2[CH2:14][CH2:13][CH:12]([N:15]3[CH2:19][CH2:18][C@H:17]([O:20][C:21]4[CH:22]=[CH:23][C:24]([C:27]([OH:29])=O)=[N:25][CH:26]=4)[C:16]3=[O:30])[CH2:11][CH2:10]2)=[N:7][CH:8]=1.O.O[C:34]1[C:42]2[N:41]=NNC=2C=[CH:36][CH:35]=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.N1CCCC1>C(Cl)Cl>[Cl:2][C:3]1[CH:4]=[C:5]([F:31])[C:6]([N:9]2[CH2:14][CH2:13][CH:12]([N:15]3[CH2:19][CH2:18][C@H:17]([O:20][C:21]4[CH:26]=[N:25][C:24]([C:27]([N:41]5[CH2:36][CH2:35][CH2:34][CH2:42]5)=[O:29])=[CH:23][CH:22]=4)[C:16]3=[O:30])[CH2:11][CH2:10]2)=[N:7][CH:8]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 67469704(S)-5-(1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)picolinic acid hydrochlorideHCID 178526939HCID 178526939, compound

Product 1

HCID 54670894(S)-1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-3-(6-(pyrrolidine-1-carbonyl)pyridin-3-yloxy)pyrrolidin-2-oneYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-5-(1-(1-(5-Chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-2-oxopyrrolidin-3-yloxy)picolinic acid hydrochloride (0.027 g, 0.062 mmol), hydroxybenzotriazole hydrate (0.013 g, 0.084 mmol), EDCI (0.016 g, 0.084 mmol), and DIEA (0.016 mL, 0.093 mmol) were stirred in CH2Cl2 (0.5 mL) for five minutes. Pyrrolidine (0.010 mL, 0.12 mmol) was added and the solution was stirred overnight at ambient temperature. The mixture was partitioned between saturated aqueous NH4Cl (20 mL) and EtOAc (40 mL). The organic phase was washed successively with saturated aqueous NaHCO3 (20 mL) and brine (20 mL). The organics were dried over MgSO4, filtered and concentrated. The residue was purified on silica (eluting with 1:24 MeOH/EtOAc) to afford (S)-1-(1-(5-chloro-3-fluoropyridin-2-yl)piperidin-4-yl)-3-(6-(pyrrolidine-1-carbonyl)pyridin-3-yloxy)pyrrolidin-2-one (24 mg, 0.049 mmol, 79%) as a colorless solid. Mass spectrum (apci) m/z=488 (M+H).

Workup

  1. customThe mixture was partitioned between saturated aqueous NH4Cl (20 mL) and EtOAc (40 mL)
  2. washThe organic phase was washed successively with saturated aqueous NaHCO3 (20 mL) and brine (20 mL)
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on silica (eluting with 1:24 MeOH/EtOAc)

Sources & evidence

ORD record
ord-191899b621bb42579d97eb0592779388
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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