Nitrogen → 7-Cyclobutyl-5-(8-fluoro-2-phenyl-quinolin-7-yl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine

HRID 244129Notes

Reaction equation

HRID 244129 reaction equation
[CH:1]1([C:5]2[N:13]3[C:8]([C:9]([NH2:14])=[N:10][CH:11]=[N:12]3)=[C:7](I)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[F:16][C:17]1[C:18](B2OC(C)(C)C(C)(C)O2)=[CH:19][CH:20]=[C:21]2[C:26]=1[N:25]=[C:24]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH:23]=[CH:22]2.C(=O)([O-])[O-].[Cs+].[Cs+].N#N.C(=O)(O)[O-].[Na+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([C:5]2[N:13]3[C:8]([C:9]([NH2:14])=[N:10][CH:11]=[N:12]3)=[C:7]([C:18]3[C:17]([F:16])=[C:26]4[C:21]([CH:22]=[CH:23][C:24]([C:27]5[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=5)=[N:25]4)=[CH:20][CH:19]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 5

HCID 947NitrogenHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 533286247-Cyclobutyl-5-iodo-imidazo[5,1-f][1,2,4]triazin-4-ylamineHCID 536290468-Fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline

Product 1

HCID 117185057-Cyclobutyl-5-(8-fluoro-2-phenyl-quinolin-7-yl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
75 °C

Procedure

A stirred solution of 7-cyclobutyl-5-iodo-imidazo[5,1-f][1,2,4]triazin-4-ylamine (40 mg, 0.1 mmol), 8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline (52 mg, 0.15 mmol) and cesium carbonate (50 mg, 0.15 mmol) in dimethoxyethane (DME) (1.67 mL) and H2O (0.33 mL) was degassed for 10 minutes using N2. Tetrakis(triphenylphosphine)palladium(0) (7 mg, 0.006 mmol) was added, and the reaction was heated to 75° C. and maintained at this temperature for 16 hours. After cooling, the reaction mixture was poured into saturated sodium bicarbonate (NaHCO3) solution (50 ml) and extracted with EtOAc (3×50 ml). The combined organics were washed with brine (2×50 ml), dried over magnesium sulfate (MgSO4), filtered and concentrated. The material was purified by chromatography on silica gel [eluting with 100% DCM→0.4% MeOH in DCM] resulting in the title compound as a white solid; 1H NMR (CDCl3, 400 MHz) δ 2.06-1.99 (m, 1H), 2.10-2.20 (m, 1H), 2.42-2.52 (m, 2H), 2.62-2.71 (m, 2H), 4.14-4.21 (m, 1H), 7.45-7.56 (m, 3H), 7.74 (d, J=8.6 Hz, 1H), 7.79 (dd, J=6.3 Hz, 6.3 Hz, 1H), 7.87 (s, 1H), 7.99 (d, J=8.8 Hz, 1H), 8.21 (d, J=6.8 Hz, 2H), 8.27 (d, J=7.6 Hz, 1H); MS (ES+): m/z 411.00 (100) [MH+], HPLC: tR=3.53 min (MicromassZQ, polar—5 min).

Workup

  1. temperaturemaintained at this temperature for 16 hours
  2. temperatureAfter cooling
  3. extractionextracted with EtOAc (3×50 ml)
  4. washThe combined organics were washed with brine (2×50 ml)
  5. dry with materialdried over magnesium sulfate (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified by chromatography on silica gel [eluting with 100% DCM→0.4% MeOH in DCM]

Sources & evidence

ORD record
ord-29cddb7a729b4908ac5053e58ec1efa7
Source dataset
uspto-grants-2014_02
Patent number
US08653268B2

Reaction notes

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