Triethylamine → N-(1-Bromoisoquinolin-3-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide

HRID 1891283Notes

Reaction equation

HRID 1891283 reaction equation
[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH2:12])[N:3]=1.CCN(CC)CC.[F:20][C:21]1([F:36])[O:25][C:24]2[CH:26]=[CH:27][C:28]([C:30]3([C:33](Cl)=[O:34])[CH2:32][CH2:31]3)=[CH:29][C:23]=2[O:22]1>ClCCl>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([NH:12][C:33]([C:30]2([C:28]3[CH:27]=[CH:26][C:24]4[O:25][C:21]([F:36])([F:20])[O:22][C:23]=4[CH:29]=3)[CH2:32][CH2:31]2)=[O:34])[N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2898451-Bromoisoquinolin-3-amineHCID 575168501-(2,2-Difluoro-1,3-benzodioxol-5-yl)cyclopropanecarbonyl chloride

Product 1

HCID 57732996N-(1-Bromoisoquinolin-3-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamideYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-bromoisoquinolin-3-amine (3.00 g, 13.5 mmol) and Et3N (3.8 mL, 27 mmol) in dichloromethane (50 mL) was added a solution of 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarbonyl chloride (4.18 g, 13.5 mmol) in dichloromethane (50 mL). The resulting reaction mixture was allowed to stir at room temperature for 18 h. The reaction mixture was then washed with 1N aqueous NaOH (2×200 mL), 1 N aqueous HCl (1×200 mL) and saturated aqueous NaHCO3 (1×200 mL). The organics were dried over sodium sulfate and evaporated. The resulting material was purified by silica gel chromatography eluting with 0-50% ethyl acetate/hexanes to yield N-(1-bromoisoquinolin-3-yl)-1-(2,2-difluorobenzo[d][1,3]-dioxol-5-yl)cyclopropanecarboxamide (4.2 g, 70%). ESI-MS m/z calc. 446.0. found 447.1 (M+1)+. Retention time 2.39 minutes.

Workup

  1. customThe resulting reaction mixture
  2. washThe reaction mixture was then washed with 1N aqueous NaOH (2×200 mL), 1 N aqueous HCl (1×200 mL) and saturated aqueous NaHCO3 (1×200 mL)
  3. dry with materialThe organics were dried over sodium sulfate
  4. customevaporated
  5. customThe resulting material was purified by silica gel chromatography
  6. washeluting with 0-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b16ce63cca2c4d89b0938cf545012a51
Source dataset
uspto-grants-2013_08
Patent number
US08507524B2

Reaction notes

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