Sodium Carbonate → HCID 67974821, compound

HRID 1502354Notes

Reaction equation

HRID 1502354 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.[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>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(#N)C>[CH3:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][C:20]=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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2734347(2,5-Dimethylphenyl)boronic acidHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide

Product 1

HCID 67974821HCID 67974821, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (49.0 mg, 168 mmol), 2,5-dimethylphenylboronic acid (52.0 mg, 347 woe, bis(di-tert-butyl(4-dimethylaminophenyl)-phosphine)dichloropalladium(II) (7.2 mg, 10 μmol) and aqueous sodium carbonate (1.0 M, 0.5 mL) and acetonitrile (1.5 mL) was heated under microwave irradiation (Biotage, 200 watts) at 120° C. for 10 minutes. The cooled reaction mixture was partitioned between ethyl acetate (20 mL) and water (20 mL), and the separated aqueous phase extracted with ethyl acetate (20 mL). The combined organic phases were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a clear oil. The crude residue was purified by reverse phase HPLC (gradient of acetonitrile in water with 0.1% formic acid) to yield the title compound as a white amorphous solid (42.3 mg, 79%). 1H NMR (400 MHz, DMSO) δ 10.88 (s, 1H), 9.16 (s, 1H), 8.48 (s, 1H), 7.98 (s, 1H), 7.89 (d, J=8.6 Hz, 1H), 7.68 (dd, J=8.5, 1.7 Hz, 1H), 7.22 (d, J=8.2 Hz, 1H), 7.15-7.11 (m, 2H), 2.33 (s, 3H), 2.23 (s, 3H), 2.12-2.03 (m, 1H), 0.91-0.78 (m, 4H). LCMS (Method E): RT=5.442 min, M+H+=317.1.

Workup

  1. customThe cooled reaction mixture
  2. customwas partitioned between ethyl acetate (20 mL) and water (20 mL)
  3. extractionthe separated aqueous phase extracted with ethyl acetate (20 mL)
  4. washThe combined organic phases were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford a clear oil
  9. customThe crude residue was purified by reverse phase HPLC (gradient of acetonitrile in water with 0.1% formic acid)

Sources & evidence

ORD record
ord-796c171a248c434b88b695b1febf8333
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

Loading…