Triethylamine → tert-Butyl 3-(methoxymethyl)-3-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)pyrrolidine-1-carboxylate

HRID 1045358Notes

Reaction equation

HRID 1045358 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:16][O:17][CH3:18])([C:13]([OH:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClCCl.C(Cl)(=O)C(Cl)=O.[Cl-].[Cl-].[F:30][C:31]([F:43])([F:42])[C:32]1[CH:33]=[N:34][C:35]2[CH2:36][CH2:37][NH:38][CH2:39][C:40]=2[CH:41]=1.C(N(CC)CC)C>ClCCl.CN(C=O)C>[CH3:18][O:17][CH2:16][C:10]1([C:13]([N:38]2[CH2:37][CH2:36][C:35]3[N:34]=[CH:33][C:32]([C:31]([F:30])([F:42])[F:43])=[CH:41][C:40]=3[CH2:39]2)=[O:15])[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 21906498HCID 21906498, compoundHCID 595695551-[(Tert-butoxy)carbonyl]-3-(methoxymethyl)pyrrolidine-3-carboxylic acidHCID 866472843-(Trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine dichloride

Product 1

HCID 59569553tert-Butyl 3-(methoxymethyl)-3-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

The title compound was prepared according to general procedure C described in connection with Scheme 2. To 1-(tert-butoxycarbonyl)-3-(methoxymethyl)pyrrolidine-3-carboxylic acid (3 g, 11.6 mmol) in dichloromethane (30 mL) was added 2M oxalyl chloride dichloromethane solution (17 mL, 34 mmole) and a few drops of DMF at room temperature. The mixture was stirred at RT for 2 hours and concentrated to dryness under the reduced pressure. 3-(Trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine dichloride (3.19 g, 11.6 mmole) in 30 dichloromethane and triethyl amine (3.1 g, 30 mmole) was added to the above residue at 0° C. The mixture was stirred at 0° C. for 1 h, diluted with dichloromethane (100 mL) and washed with sodium bicarbonate solution (2×50 mL) and water (3×100 mL), dried over sodium sulfate and purified by silica chromatography using 2.5% MeOH in CH2Cl2 as eluent to give product (1.7 g, 33% yield). 1H NMR (400 MHz, CD3OD): δ 8.70 (s, 1H), 7.68 (m, 1H), 4.80 (s, 2H), 4.10-2.95 (m, 13H), 2.40-2.15 (m, 2H), 1.48 (s, 9H); MS (ESI) m/z: Calculated for C21H28F3N3O4: 443.2. found: 466 (M+Na)+.

Workup

  1. concentrationconcentrated to dryness under the reduced pressure
  2. stirringThe mixture was stirred at 0° C. for 1 h
  3. washwashed with sodium bicarbonate solution (2×50 mL) and water (3×100 mL)
  4. dry with materialdried over sodium sulfate
  5. custompurified by silica chromatography

Sources & evidence

ORD record
ord-1dab4e8ccf2144cdab893d2529d14232
Source dataset
uspto-grants-2013_10
Patent number
US08569282B2

Reaction notes

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