Nitrogen → HCID 86696420, compound

HRID 870717Notes

Reaction equation

HRID 870717 reaction equation
[CH:1]([O:4][C:5](=[O:23])[N:6]([CH2:10][CH2:11][NH:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19](Br)=[CH:20][N:21]=2)[N:18]=1)[CH:7]([CH3:9])[CH3:8])([CH3:3])[CH3:2].[CH:24]1([B-](F)(F)F)[CH2:26][CH2:25]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl.N#N>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH:1]([O:4][C:5](=[O:23])[N:6]([CH2:10][CH2:11][NH:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH:24]3[CH2:26][CH2:25]3)=[CH:20][N:21]=2)[N:18]=1)[CH:7]([CH3:9])[CH3:8])([CH3:3])[CH3:2]

Participants

9

Reactant 5

HCID 947Nitrogen2×HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 23697338Potassium cyclopropyltrifluoroborateHCID 86696421HCID 86696421, compound

Product 1

HCID 86696420HCID 86696420, compoundYield 9%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 10% (v/v) water in THF (25 mL) was added to a mixture of [2-(3-bromo-imidazo[1,2-b]pyridazin-6-ylamino)-ethyl]-isopropyl-carbamic acid isopropyl ester (515.1 mg, 1.34 mmol), potassium cyclopropyltrifluoroborate [1065010-87-1] (396.8 mg, 2.7 mmol), cesium carbonate [534-17-8] (1.3 g, 4.0 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane [95464-05-4] (110.4 mg, 0.1 mmol) contained in a 50 mL round bottomed flask. The reaction pot was fitted to a reflux condenser and the system taken through 10 evacuation/N2 blanket cycles while being rapidly stirred. The rapidly stirred, N2 blanketed, reaction was heated reflux for 4d then cooled and filtered. The filtrate was partitioned between brine and ethyl acetate and the phase separated organic extract dried (MgSO4) and evaporated to give a black oil which was purified by preparatory RP-HPLC to provide 41.6 mg of [2-(3-cyclopropyl-imidazo[1,2-b]pyridazin-6-ylamino)-ethyl]-isopropyl-carbamic acid isopropyl ester as a white solid. 1H NMR (400 MHz, METHANOL-d4) δ ppm 0.77-0.84 (m, 2H) 0.98-1.06 (m, 2H) 1.20-1.32 (m, 14H) 2.08-2.19 (m, 1H) 3.43-3.50 (m, 2H) 3.50-3.59 (m, 2H) 6.61 (d, J=9.70 Hz, 1H) 7.08 (s, 1H) 7.52 (d, J=9.70 Hz, 1H). LRMS (ESI) m/z 346.2 [(M+H)]+, calc'd for C18H27N6O2: 345.45.

Workup

  1. customcontained in a 50 mL round bottomed flask
  2. customThe reaction
  3. custompot was fitted to a reflux condenser
  4. stirringThe rapidly stirred
  5. customreaction
  6. temperaturewas heated
  7. temperaturethen cooled
  8. filtrationfiltered
  9. customThe filtrate was partitioned between brine and ethyl acetate
  10. customthe phase separated organic
  11. extractionextract
  12. dry with materialdried (MgSO4)
  13. customevaporated
  14. customto give a black oil which
  15. customwas purified by preparatory RP-HPLC

Sources & evidence

ORD record
ord-c62242eff3ea4ef4a22da8e4bc1e01ad
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

Loading…