Triethylamine → HCID 59569572, compound

HRID 1045351Notes

Reaction equation

HRID 1045351 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:16][CH:17]2[CH2:19][CH2:18]2)([C:13]([OH:15])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O.Cl.[F:25][C:26]([F:38])([F:37])[C:27]1[CH:28]=[N:29][C:30]2[CH2:31][CH2:32][NH:33][CH2:34][C:35]=2[CH:36]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[CH:17]1([CH2:16][C:10]2([C:13]([N:33]3[CH2:32][CH2:31][C:30]4[N:29]=[CH:28][C:27]([C:26]([F:25])([F:37])[F:38])=[CH:36][C:35]=4[CH2:34]3)=[O:15])[CH2:11][CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)[CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 59447818HCID 59447818, compoundHCID 601460143-(Trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine--hydrogen chloride (1/1)

Product 1

HCID 59569572HCID 59569572, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared according to general procedure C described in connection with Scheme 5. To a solution of 1-(t-butoxycarbonyl)-3-(cyclopropylmethyl)pyrrolidine-3-carboxylic acid IIIb (300 mg, 1.11 mmol) in 16 mL of CH2Cl2 was added thionyl chloride (0.24 mL, 3.34 mmol) and two drops of DMF. The mixture was stirred for ˜1-2 h at room temperature. After removal of solvent, the residue was redissolved in CH2Cl2 (13 mL), followed by the addition of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine hydrochloride (IVa) (320 mg, 1.16 mmol) and triethyl amine (0.78 mL, 5.5 mmol). LC-MS analysis indicated the completion of the reaction after one hour stirring at RT. The mixture was washed with water (×2) and brine (×3). After concentration of solvent, the crude residue was purified by flash chromatography on silica gel to give 300 mg (60% yield) of the desired product. MS (ESI) m/z: Calculated for C23H30F3N3O3: 453.2. found: 453.7 (M+Na)+.

Workup

  1. customThe title compound was prepared
  2. customAfter removal of solvent
  3. dissolutionthe residue was redissolved in CH2Cl2 (13 mL)
  4. customthe completion of the reaction after one hour
  5. stirringstirring at RT
  6. washThe mixture was washed with water (×2) and brine (×3)
  7. customAfter concentration of solvent, the crude residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-fd5fb29fc82f4a4abdc764099a3273ec
Source dataset
uspto-grants-2013_10
Patent number
US08569282B2

Reaction notes

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