Potassium Carbonate → 9-tert-butyl-2-(3-pyridyl)-14-(3,6-dihydro-2H-pyran-4-yl)-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

HRID 1971756Notes

Reaction equation

HRID 1971756 reaction equation
[C:1]([N:5]1[CH2:32][CH2:31][CH2:30][CH2:29][C:8]2[C:9](Br)=[C:10]3[C:19]4[CH:18]=[C:17]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[C:16]([O:26][CH3:27])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:33])([CH3:4])([CH3:3])[CH3:2].[O:34]1[CH2:39][CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH2:36][CH2:35]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.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>[C:1]([N:5]1[CH2:32][CH2:31][CH2:30][CH2:29][C:8]2[C:9]([C:37]3[CH2:38][CH2:39][O:34][CH2:35][CH:36]=3)=[C:10]3[C:19]4[CH:18]=[C:17]([C:20]5[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=5)[C:16]([O:26][CH3:27])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:33])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 581248489-tert-butyl-2-(3-pyridyl)-14-bromo-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

Product 1

HCID 581249569-tert-butyl-2-(3-pyridyl)-14-(3,6-dihydro-2H-pyran-4-yl)-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 75 mg of 25b, 37 mg of 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5,-tetramethyl-1,3,2-dioxaborolane, 41 mg of K2CO3 and 17 mg of tetrakis(triphenylphosphine)palladium(0) in 3 ml of degassed DMF was heated under N2 atmosphere at 125° C. for 2 hr. The reaction was cooled and diluted with 15 ml of water. The product was extracted with ethyl acetate. The organic extract was washed with water, dried and concentrated. The remainder was chromatographed over silcagel (using a gradient of heptane/acetone as eluent). The product isolated was triturated with diethyl ether, providing 57 mg of white crystalline 25c; Mp 208-210° C. LC-MS-ESI: [M+1] 512.13. NMR (CDCl3) δ 8.70, 8.58, 7.88, and 7.37 (4×m, 4, pyridine-H), 7.68 and 6.87 (2×s, 2, Ar—H), 1.60 (s, 9, tertC4H9), 3.87 (s, 3, OCH3), 5.75 (m, 1, CH), 4.30 (m, 2, CH2O), 4.70 (bm, 1, CH2), 3.55 (bm, 1, CH), 3.85 (bm, 4, 2×CH2) 3.00 and 3.20 (2×bm, 2, CH2), 2.63 (bm, 2, CH2), 2.35 (m, 2, CH2), 1.70-2.05 (bm, 4, 2×CH2).

Workup

  1. temperatureThe reaction was cooled
  2. extractionThe product was extracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with water
  5. customdried
  6. concentrationconcentrated
  7. customThe remainder was chromatographed over silcagel (
  8. customThe product isolated
  9. customwas triturated with diethyl ether

Sources & evidence

ORD record
ord-42366e2fb7a544eea4dcccdd3917d0a3
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

Loading…