Triethylamine → [1-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridine-6-carbonyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

HRID 406464Notes

Reaction equation

HRID 406464 reaction equation
[I-].[C:2]([O:6][C:7]([NH:9][CH:10]1[CH2:14][CH2:13][N:12]([C:15]([N:17]2[CH:21]=[CH:20][N+](C)=[CH:18]2)=[O:16])[CH2:11]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].[F:23][C:24]([F:36])([F:35])[C:25]1[CH:26]=[N:27][C:28]2CCNC[C:33]=2[CH:34]=1.CCN(CC)CC>C(Cl)Cl>[C:2]([O:6][C:7](=[O:8])[NH:9][CH:10]1[CH2:14][CH2:13][N:12]([C:15]([N:17]2[CH2:18][CH2:33][C:28]3[N:27]=[CH:26][C:25]([C:24]([F:36])([F:35])[F:23])=[CH:34][C:20]=3[CH2:21]2)=[O:16])[CH2:11]1)([CH3:3])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 114810975,6,7,8-Tetrahydro-3-(trifluoromethyl)-1,6-naphthyridineHCID 866217213-(3-tert-butoxycarbonylamino-pyrrolidine-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide

Product 1

HCID 59764725[1-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridine-6-carbonyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(3-tert-butoxycarbonylamino-pyrrolidine-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide (preparation #4) (7.81 g, 18.5 mmol) in DCM (70 mL) was added 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,6]naphthyridine (3.74 g, 18.5 mmol) and Et3N (2.6 mL, 18.5 mmol) and the reaction mixture was stirred at ambient temperature for about 16 h. Additional Et3N (1.5 mL, 10.7 mmol) was added and the reaction mixture was stirred at ambient temperature for about 16 h. The reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography on silica gel using 5% MeOH/DCM as the mobile phase to give [1-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridine-6-carbonyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (4.91 g, 64%). RP-HPLC (Table 1, Method a) Rt 2.37 min; m/z: (M+H)+ 415.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for about 16 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue was purified by flash chromatography on silica gel using 5% MeOH/DCM as the mobile phase

Sources & evidence

ORD record
ord-7322c4951d6148f88f5b99865f247943
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

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