Potassium Carbonate → HCID 71255614, compound

HRID 540183Notes

Reaction equation

HRID 540183 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](OC(F)(F)F)[CH:10]=2)[N:5]=[C:4]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[S:20](=[O:29])(=[O:28])[CH2:19][CH2:18]2)[CH:3]=1.[O:30]=[C:31]1[NH:35][CH2:34][CH:33]([C:36]([NH2:38])=[O:37])[CH2:32]1.[C:39](=O)([O-])[O-].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>ClCCl.[Cu]I.COCCOCCOC>[O:29]=[S:20]1(=[O:28])[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[CH2:23][N:17]([C:4]2[CH:3]=[C:2]([NH:38][C:36]([CH:33]3[CH2:32][C:31](=[O:30])[NH:35][CH2:34]3)=[O:37])[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:39])[CH:10]=3)[N:5]=2)[CH2:18][CH2:19]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 35285145-oxopyrrolidine-3-carboxamideHCID 712545694-(4-Chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71255614HCID 71255614, compoundYield 3.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolventHCID 8150DiglymeSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 4-(4-bromo-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (500 mg, 1.19 mol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1), 5-oxopyrrolidine-3-carboxamide (307 mg, 2.39 mmol), copper(I) iodide (23 mg, 0.12 mmol), potassium carbonate (497 mg, 3.60 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (0.038 mL, 0.24 mmol) and diethylene glycol dimethyl ether (10 mL) was heated with stirring in a 10 mL microwave process vial for 3 hours at 140° C. under microwave irridiation. The mixture was diluted with dichloromethane, washed with water. The aqueous layer was back extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give 40 mg of N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-5-oxopyrrolidine-3-carboxamide as light brown solid. MS obsd. (ESI+) [(M+H)+] 451, 1H NMR (400 MHz, DMSO-d6) δ ppm 9.98 (s, 1 H), 7.88 (m, 3 H), 7.81 (s, 1 H), 7.70 (s, 1 H), 7.64 (td, J=1.2, 7.6 Hz, 1 H), 7.47 (d, J=8.8 Hz, 1 H), 7.46 (dd, J=0.8, 7.6 Hz, 1 H), 7.38 (dd, J=1.6, 8.4 Hz, 1 H), 5.08 (s, 2 H), 4.42 (brs, 2 H), 3.73-3.57 (m, 4 H), 3.43 (dd, J=6.0, 9.6 Hz, 1 H), 3.32 (s, 1 H), 2.48 (m, 1 H), 2.42 (s, 3 H).

Workup

  1. temperaturewas heated
  2. washwashed with water
  3. extractionThe aqueous layer was back extracted with dichloromethane
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-3dcdc1b0e6114a1b80976cee217d17a4
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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