Triethylamine → (3-hydroxy-pyrrolidin-1-yl)-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-methanone

HRID 406463Notes

Reaction equation

HRID 406463 reaction equation
[I-].C[N+]1[CH:7]=[CH:6][N:5]([C:8]([N:10]2[CH2:19][CH2:18][C:17]3[N:16]=[CH:15][C:14]([C:20]([F:23])([F:22])[F:21])=[CH:13][C:12]=3[CH2:11]2)=[O:9])[CH:4]=1.N1CC[CH:26]([OH:29])C1.CCN(CC)CC>C(Cl)Cl>[OH:29][CH:26]1[CH2:7][CH2:6][N:5]([C:8]([N:10]2[CH2:19][CH2:18][C:17]3[N:16]=[CH:15][C:14]([C:20]([F:21])([F:23])[F:22])=[CH:13][C:12]=3[CH2:11]2)=[O:9])[CH2:4]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 982104-HydroxypyrrolidineHCID 866217201-methyl-3-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridine-6-carbonyl)-3H-imidazol-1-ium iodide

Product 1

HCID 59764984(3-hydroxy-pyrrolidin-1-yl)-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-methanoneYield 34.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-methyl-3-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridine-6-carbonyl)-3H-imidazol-1-ium iodide (preparation #3) (0.046 g, 0.10 mmol) in DCM (1 mL) was added pyrrolidin-3-ol (0.009 g, 0.10 mmol) and Et3N (0.014 mL, 0.10 mmol) and the reaction mixture was shaken at ambient temperature for about 30 min. The reaction mixture was dried in vacuo (Genevac®) and the residue purified by RP-HPLC (10% acetonitrile/0.05M aqueous ammonium acetate, buffered to pH 4.5 for 3 min., 10% to 65% acetonitrile/0.05M aqueous ammonium acetate over 6 min at 22.5 mL/min with 2.5 mL/min. acetonitrile at-column dilution; APCI positive mode detection; Xterra prep. MS C18. 19×50 mm column) to afford (3-hydroxy-pyrrolidin-1-yl)-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-methanone (0.011 g, 33%). RP-HPLC (Table 1, Method a) Rt 1.72 min; m/z: (M+H)+ 316.

Workup

  1. customThe reaction mixture was dried in vacuo (Genevac®)
  2. customthe residue purified by RP-HPLC (10% acetonitrile/0.05M aqueous ammonium acetate, buffered to pH 4.5 for 3 min., 10% to 65% acetonitrile/0.05M aqueous ammonium acetate over 6 min at 22.5 mL/min with 2.5 mL/min. acetonitrile at-column dilution; APCI positive mode detection; Xterra prep. MS C18. 19×50 mm column)

Sources & evidence

ORD record
ord-a3d62396afcd40b88c2cd8381fa4ea30
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

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