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

HRID 1971736Notes

Reaction equation

HRID 1971736 reaction equation
[C:1]([N:5]1[CH2:27][CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Cl:23])=[C:10]3[C:19]4[CH:18]=[C:17](Br)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:28])([CH3:4])([CH3:3])[CH3:2].[N:29]1[CH:34]=[CH:33][CH:32]=[C:31](B(O)O)[CH:30]=1.C([O-])([O-])=O.[K+].[K+].C(COC)OC>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[CH2:27][CH2:26][CH2:25][CH2:24][C:8]2[C:9]([Cl:23])=[C:10]3[C:19]4[CH:18]=[C:17]([C:31]5[CH:30]=[N:29][CH:34]=[CH:33][CH:32]=5)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:28])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 581249549-tert-butyl-3-methoxy-2-bromo-14-chloro-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

Product 1

HCID 509061449-tert-butyl-3-methoxy-2-pyridin-3-yl-14-chloro-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 65 mg of 19e, 25 mg of 3-pyridine-boronic acid, 45 mg of K2CO3 and 12 mg of Pd(PPh3)4 in 3 ml of degassed 90% aq. dimethoxyethane was heated under a nitrogen atmosphere for 16 h at 90° C. The mixture was diluted with water, extracted with ethyl acetate, dried and concentrated. The residues were purified by chromatography over silica gel, using a gradient of heptane/ethyl acetate as eluent. The material thus obtained was triturated with pentane, to provide 45 mg of white crystalline 19f; Mp: 190-192° C. MS-ESI: [M+1] 464.17, 465.17 and 466.17. NMR (CDCl3) δ 1.58 (s, 3, tertC4H9), 1.62-1.77 (bm, 2, CH2), 1.80-2.05 (bm, 2, CH2), 2.60-2.77 (bm, 2, CH2), 2.970-3.18 (bm, 2, CH2), 3.50 bm, 1, CH), 3.76-3.92 (bm, 2, CH2), 3.86 (s, 3, OCH3), 4.50 (bm, 1, CH), 6.87 (s, 1, ArH), 8.20 (s, 1, ArH), 7.36, 7.89, 8.57, 8.83 (4×m, 4, pyridine-H).

Workup

  1. extractionextracted with ethyl acetate
  2. customdried
  3. concentrationconcentrated
  4. customThe residues were purified by chromatography over silica gel
  5. customThe material thus obtained
  6. customwas triturated with pentane

Sources & evidence

ORD record
ord-3067f6d3a90d452f93594f80868ab843
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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