1,2-Dichloroethane → HCID 57410729, compound

HRID 1502261Notes

Reaction equation

HRID 1502261 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.C(OC([N:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[B-](F)(F)F)=O)(C)(C)C.[K+].C(#N)C.O.C(=O)([O-])[O-].[K+].[K+].ClCCCl.FC(F)(F)C(O)=O>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.C(OCC)(=O)C>[NH:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1

Participants

10

Reactant 7

HCID 111,2-DichloroethaneHCID 962WaterHCID 6342AcetonitrileHCID 6422Trifluoroacetic acid2×HCID 11430Potassium CarbonateHCID 25212873HCID 25212873, compoundHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 57410729HCID 57410729, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (116.6 mg, 0.4005 mmol) and potassium (1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl)trifluoroborate (215 mg, 0.787 mmol) was added acetonitrile (3 mL, 60 mmol) and water (0.3 mL, 20 mmol). Potassium carbonate (173.6 mg, 1.256 mmol) and bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (13.4 mg, 0.0189 mmol) were added and the reaction was stirred in a sealed vial at 90° C. for two hours. The reaction mixture was then poured into ethyl acetate, which was washed with two portions water, dried with brine and MgSO4, filtered, and evaporated in vacuo. The resulting residue was dissolved in 1,2-dichloroethane (3 mL, 40 mmol), and trifluoroacetic acid (0.30 mL, 3.9 mmol) was added. The mixture was stirred at room temperature for 15 hours, and then trifluoroacetic acid (1.0 mL) was added and the mixture was stirred at 40° C. for 4 hours. The reaction mixture was evaporated in vacuo, dissolved in dichloromethane and washed once with saturated aqueous NaHCO3. The organic portion was dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 17.4 mg (16%) of N-(7-(1H-pyrrol-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (Min)=4.073, M+H=278.0, method=E; 1H NMR (400 MHz, DMSO-d6) δ 11.49 (s, 1H), 10.81 (s, 1H), 9.02 (s, 1H), 8.39 (s, 1H), 8.17 (s, 1H), 7.99 (d, J=8.7 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 6.93 (s, 1H), 6.67 (s, 1H), 6.17 (s, 1H), 2.15-1.99 (m, 1H), 0.84 (m, 4H).

Workup

  1. washwas washed with two portions water
  2. dry with materialdried with brine and MgSO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. stirringThe mixture was stirred at room temperature for 15 hours
  6. stirringthe mixture was stirred at 40° C. for 4 hours
  7. customThe reaction mixture was evaporated in vacuo
  8. dissolutiondissolved in dichloromethane
  9. washwashed once with saturated aqueous NaHCO3
  10. dry with materialThe organic portion was dried over MgSO4
  11. filtrationfiltered
  12. customevaporated in vacuo
  13. customThe crude product was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-d9b4d09f515c49b094adf32f149c33a2
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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