Potassium Carbonate → 1-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(6-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 1471848Notes

Reaction equation

HRID 1471848 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:12][C:13]([C:15]2([C:18]3[CH:28]=[CH:27][C:21]4[O:22][C:23]([F:26])([F:25])[O:24][C:20]=4[CH:19]=3)[CH2:17][CH2:16]2)=[O:14])[N:3]=1.[CH3:29][O:30][C:31]1[N:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC>[F:25][C:23]1([F:26])[O:22][C:21]2[CH:27]=[CH:28][C:18]([C:15]3([C:13]([NH:12][C:4]4[N:3]=[C:2]([C:34]5[CH:35]=[N:36][C:31]([O:30][CH3:29])=[CH:32][CH:33]=5)[C:11]5[C:6]([CH:5]=4)=[CH:7][CH:8]=[CH:9][CH:10]=5)=[O:14])[CH2:17][CH2:16]3)=[CH:19][C:20]=2[O:24]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 57732996N-(1-Bromoisoquinolin-3-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

Product 1

HCID 577330101-(2,2-Difluorobenzo[d][1,3]dioxol-5-yl)-N-(1-(6-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamideYield 71.5%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

N-(1-Bromoisoquinolin-3-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (268 mg, 0.600 mmol) was dissolved in 6 mL of 1,2-dimethoxyethane (DME) in a microwave reactor tube. 6-Methoxypyridin-3-ylboronic acid (119 mg, 0.780 mmol), 0.6 mL of an aqueous 2 M potassium carbonate solution, and tetrakis(triphenylphospine)palladium(0) (Pd(PPh3)4, 34.7 mg, 0.0300 mmol) were added and the reaction mixture was heated at 120° C. in a microwave reactor for 20 minutes. The resulting material was cooled to room temperature, filtered, and the layers were separated. The crude product was evaporated to dryness and then purified on silica gel utilizing a gradient of 0-50% ethyl acetate in hexanes to yield 1-(2,2-difluorobenzo-[d][1,3]dioxol-5-yl)-N-(1-(6-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropane-carboxamide (204 mg, 71%). ESI-MS m/z calc. 475.1. found; 476.3 (M+1)+ Retention time 2.31 minutes.

Workup

  1. temperatureThe resulting material was cooled to room temperature
  2. filtrationfiltered
  3. customthe layers were separated
  4. customThe crude product was evaporated to dryness
  5. custompurified on silica gel utilizing a gradient of 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f25a69b569d0450ea8b2424b1238ca17
Source dataset
uspto-grants-2015_04
Patent number
US09012473B2

Reaction notes

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