Potassium Carbonate → HCID 24751510, compound

HRID 1713096Notes

Reaction equation

HRID 1713096 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11](=[O:32])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18](B5OC(C)(C)C(C)(C)O5)[CH:19]=4)[CH2:14]3)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.Br[C:34]1C=C[C:37](=[O:41])[N:38](C)[CH:39]=1.C([O-])([O-])=[O:43].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11](=[O:32])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([N:38]5[CH2:39][CH2:34][O:43][C:37]5=[O:41])[CH:19]=4)[CH2:14]3)[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 130240275-Bromo-1-methylpyridin-2(1H)-oneHCID 59463632HCID 59463632, compound

Product 1

HCID 24751510HCID 24751510, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a sealed tube charged with 2-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline (1.00 g, 2.28 mmol), 5-bromo-1-methylpyridin-2(1H)-one (513 mg, 2.73 mmol, 1.2 eq.), Pd(PPh3)4 (100 mg, 0.087 mmol, 0.04 eq.) and K2CO3 (945 mg, 6.84 mmol, 3.0 eq.), are added dioxane (20 ml) and water (3 mL). The mixture is degassed with nitrogen for 5 min. The tube is sealed and heated at 100° C. overnight. The reaction mixture is cooled and partitioned between DCM (150 mL) and 1N NaOH (100 mL). The mixture is extracted with DCM (2×150 mL). The combined organic extracts are dried and evaporated to yield the crude product which is purified by silica gel column chromatography eluting with EtOAc/MeOH/NEt3 (95:5:3) to yield the title compound. 1H NMR (300 MHz, CDCl3) δ 7.61 (1H, dd), 7.47 (1H, d), 7.15 (1H, s), 7.06 (1H, d), 6.66 (1H, d), 3.72 (2H, s), 3.67-3.64 (m, 4H), 3.62 (3H, s), 3.37 (2H, s), 2.94 (2H, t), 2.81 (2H, t), 2.69 (1H, m), 2.32-2.27 (4H, m), 2.03-1.67 (6H); MS (+VE) m/z 421.49 (M++1).

Workup

  1. customThe mixture is degassed with nitrogen for 5 min
  2. customThe tube is sealed
  3. temperatureThe reaction mixture is cooled
  4. custompartitioned between DCM (150 mL) and 1N NaOH (100 mL)
  5. extractionThe mixture is extracted with DCM (2×150 mL)
  6. customThe combined organic extracts are dried
  7. customevaporated
  8. customto yield the crude product which
  9. customis purified by silica gel column chromatography
  10. washeluting with EtOAc/MeOH/NEt3 (95:5:3)

Sources & evidence

ORD record
ord-bdf70a05c9134c15b8683fe6ff80d1c2
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

Loading…