Morpholine → HCID 178512318, compound

HRID 1887949Notes

Reaction equation

HRID 1887949 reaction equation
[NH2:1][CH2:2][C:3]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][C:8]([Cl:14])=[CH:9][CH:10]=2)[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:4]=1.[CH:21]([N:24]([CH2:28]C)C(C)C)(C)C.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.C[N:37]1C(=O)CCC1>>[Cl:14][C:8]1[CH:7]=[C:6]2[C:11]([C:12](=[O:13])[C:3]([CH2:2][NH:1][C:21]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[N:24][C:28]#[N:37])=[CH:4][N:5]2[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[CH:10][CH:9]=1

Participants

5

Reactant 4

HCID 8083MorpholineHCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 712083983-(aminomethyl)-7-chloro-1-phenylquinolin-4(1H)-one2×

Product 1

HCID 178512318HCID 178512318, compoundYield 56%

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 3-(aminomethyl)-7-chloro-1-phenylquinolin-4(1H)-one (intermediate D) (30 mg, 0.105 mmol) and N,N-diisopropylethylamine (40.9 mg, 55.2 μL, 0.316 mmol) in NMP (0.5 mL) was added diphenyl-cyanocarbonimidate (25.1 mg, 0.105 mmol). After 1 hr., morpholine (11.9 mg, 12.0 μL, 0.137 mmol) was added and the mixture was warmed to 120° C. in a sealed microwave tube. After 1 hr., LCMS showed complete conversion to product. The mixture was allowed to cool to room temp. and the crude product was purified using preparative reverse-phase HPLC. The product [(7-chloro-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amino]-morpholin-4-yl-methylene-cyan-amide (25 mg, 56%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.26 (d, J=8.8 Hz, 1H) 8.07 (s, 1H) 7.61-7.76 (m, 3H) 7.57-7.62 (m, 2H) 7.48-7.53 (m, 1H) 7.46 (dd, J=8.8, 1.9 Hz, 1H) 6.93 (d, J=1.9 Hz, 1H) 4.36 (d, J=4.8 Hz, 2H) 3.51-3.62 (m, 4H) 3.35-3.46 (m, 4H).

Workup

  1. waitAfter 1 hr
  2. temperatureto cool to room temp.
  3. customthe crude product was purified

Sources & evidence

ORD record
ord-c57faa0f0dc74001a9a23d03bd8563b4
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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