Nitrogen → 3-Cyclobutyl-1-(2-pyridin-4-ylquinolin-7-yl)imidazo[1,5-a]pyrazin-8-ylamine

HRID 386223Notes

Reaction equation

HRID 386223 reaction equation
N#N.Br[C:4]1[N:5]=[C:6]([CH:14]2[CH2:17][CH2:16][CH2:15]2)[N:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[C:8]=12.[N:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][C:28](B4OC(C)(C)C(C)(C)O4)=[CH:29][CH:30]=3)[N:25]=2)=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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:14]1([C:6]2[N:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[C:8]3=[C:4]([C:28]3[CH:27]=[C:26]4[C:31]([CH:32]=[CH:33][C:24]([C:21]5[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=5)=[N:25]4)=[CH:30][CH:29]=3)[N:5]=2)[CH2:17][CH2:16][CH2:15]1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 576809341-Bromo-3-cyclobutylimidazo[1,5-a]pyrazin-8-amineHCID 576809362-Pyridin-4-yl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline

Product 1

HCID 116325683-Cyclobutyl-1-(2-pyridin-4-ylquinolin-7-yl)imidazo[1,5-a]pyrazin-8-ylamine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

N2 was bubbled into a stirred mixture of 1-bromo-3-cyclobutylimidazo[1,5-a]pyrazin-8-ylamine (48 mg, 0.18 mmol), 2-pyridin-4-yl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)quinoline (90 mg, 0.27 mmol), Pd(PPh3)4 (12.5 mg, 0.0108 mmol), and Na2CO3 (48 mg, 0.45 mmol) in DMF/H2O (5/1, 6 mL) for 5 min. This mixture was then stirred at 80° C. under N2 for 40 h. The solvents were removed; the residue was dissolved in MeOH and submitted to the mass-directed purification system and provided the desired product; 1H-NMR (CDCl3, 400 MHz) δ 2.02-2.10 (m, 1 H), 2.17-2.24 (m, 1 H), 2.50-2.57 (m, 2 H), 2.62-2.70 (m, 2 H), 3.84-3.89 (m, 1 H), 5.45 (s, br, 2 H), 7.10 (d, J=4.4 Hz, 1 H), 7.17 (d, J=5.2 Hz, 1 H), 7.96 (d, J=8.8 Hz, 1 H), 8.00-8.01 (m, 2 H), 8.10 (d, J=6.0 Hz, 2 H), 8.35 (d, J=8.4 Hz, 1 H), 8.45 (s, 1 H), 8.80 (d, J=4.8 Hz, 2 H); MS (ES+): m/z 393 [MH+]; HPLC: tR=1.94 min (OpenLynx, polar—5 min).

Workup

  1. customThe solvents were removed
  2. dissolutionthe residue was dissolved in MeOH

Sources & evidence

ORD record
ord-9ef005bb1a5e42a6b0242e58a37ae529
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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