Diisopropylethylamine → {1-[3-(5,6,7,8-Tetrahydro-[1,8]-naphthyridin-2-ylmethyl)-pyrrolidine-1-carbonyl]-piperidin-4-yl}-acetic acid ethyl ester

HRID 277888Notes

Reaction equation

HRID 277888 reaction equation
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.ClC(Cl)(O[C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[N:35]1[C:44]2[NH:43][CH2:42][CH2:41][CH2:40][C:39]=2[CH:38]=[CH:37][C:36]=1[CH2:45][CH:46]1[CH2:50][CH2:49][NH:48][CH2:47]1>CC#N.CN(C=O)C>[CH2:12]([O:11][C:9](=[O:10])[CH2:8][CH:5]1[CH2:6][CH2:7][N:2]([C:27]([N:48]2[CH2:49][CH2:50][CH:46]([CH2:45][C:36]3[CH:37]=[CH:38][C:39]4[CH2:40][CH2:41][CH2:42][NH:43][C:44]=4[N:35]=3)[CH2:47]2)=[O:33])[CH2:3][CH2:4]1)[CH3:13]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 120171643-(5,6,7,8-Tetrahydro-[1,8]naphthyridin-2-ylmethyl)-pyrrolidineHCID 45358839Piperidin-4-yl-acetic acid ethyl ester hydrochloride

Product 1

HCID 70160755{1-[3-(5,6,7,8-Tetrahydro-[1,8]-naphthyridin-2-ylmethyl)-pyrrolidine-1-carbonyl]-piperidin-4-yl}-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent2×

Procedure

To a solution of 6-2 (31 mg, 0.15 mmol), DIPEA (77 μL, 0.44 mmol), and CH3CN (1.5 mL) at 0° C. was added dropwise a solution of triphosgene (15 mg, 52 mmol) in CH3CN (150 μL). Afer 30 min., a solution of 1-8 (43 mg, 0.15 mmol) and DIPEA (77 μL, 0.44 mmol) in DMF (0.8 mL) was added, followed by removal of the cooling bath. After 16 hrs, the reaction mixture was poured into EtOAc and sat. NaHCO3. The EtOAc portion was then washed with H2O and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 10% ethanol/EtOAc) gave 6-3 as a colorless oil.

Workup

  1. customfollowed by removal of the cooling bath
  2. additionthe reaction mixture was poured into EtOAc and sat. NaHCO3
  3. washThe EtOAc portion was then washed with H2O and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8d616ea15c564bee8b112111b05b7320
Source dataset
uspto-grants-2002_03
Patent number
US06358970B1

Reaction notes

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