Potassium Carbonate → 6-Methyl-2-oxo-1-(2-pyrrolidin-1-yl-ethyl)-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-quinolin-3-carbonitrile

HRID 346642Notes

Reaction equation

HRID 346642 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[C:6]([C:13]#[N:14])=[C:5]2[N:15]1[CH2:20][CH2:19][N:18]([C:21]([C:23]2[S:24][CH:25]=[CH:26][CH:27]=2)=[O:22])[CH2:17][CH2:16]1.Cl.Cl[CH2:30][CH2:31][N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:30][CH2:31][N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1)[C:7](=[O:12])[C:6]([C:13]#[N:14])=[C:5]2[N:15]1[CH2:16][CH2:17][N:18]([C:21]([C:23]2[S:24][CH:25]=[CH:26][CH:27]=2)=[O:22])[CH2:19][CH2:20]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 210819836-Methyl-2-oxo-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-quinolin-3-carbonitrile

Product 1

HCID 210819826-Methyl-2-oxo-1-(2-pyrrolidin-1-yl-ethyl)-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1,2-dihydro-quinolin-3-carbonitrileYield 19%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of Compound 107 (1 g., 2.64 mmol), 1-(2-chloroethyl) pyrrolidine hydrochloride (2.24 g, 13.2 mmol), and potassium carbonate (3.64 g, 26.4 mmol) in DMF was heated overnight at 90° C. The solution was cooled and poured into ice water. The solids formed were filtered, washed by water, and dried. The crude product was purified by flash chromatography eluting with 0–10% methanol in ethylacetate gradient to yield 236 mg (19%) of pale yellow solids. M.P. 139–143° C. 1H NMR (DMSO-d6): δ 1.67 (m, 4H), 2.41 (s, 3H), 2.53 (m, 4H), 2.61 (m, 2H), 3.01 (m, 2H), 3.62 (m, 4H), 3.93 (m, 4H), 4.30 (m, 2H), 7.16 (dd, J=3.4, 4.8 Hz, 1H), 7.49 (m, 2H), 7.60 (m, 1H), 7.69 (s, 1H), 7.80 (d, J=5.2 Hz, 1H). EIMS m/z 476 (M+1). Anal. (C26H29N5O2S) C, H, N.

Workup

  1. temperatureThe solution was cooled
  2. customThe solids formed
  3. filtrationwere filtered
  4. washwashed by water
  5. customdried
  6. customThe crude product was purified by flash chromatography
  7. washeluting with 0–10% methanol in ethylacetate gradient

Sources & evidence

ORD record
ord-0b1029b30de54beb8ebaa10f743ee070
Source dataset
uspto-grants-2007_02
Patent number
US07173036B2

Reaction notes

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