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

HRID 386224Notes

Reaction equation

HRID 386224 reaction equation
[CH:1]1([C:5]2[N:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7](I)[N:6]=2)[CH2:4][CH2:3][CH2:2]1.[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:27][CH:28]=2)[N:23]=1.C([O-])([O-])=O.[Na+].[Na+].O>CN(C=O)C.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:9]3[CH:10]=[CH:11][N:12]=[C:13]([NH2:14])[C:8]3=[C:7]([C:26]3[CH:25]=[C:24]4[C:29]([CH:30]=[CH:31][C:22]([C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][N:16]=5)=[N:23]4)=[CH:28][CH:27]=3)[N:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 426093653-Cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-amineHCID 576810172-Pyridin-2-yl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline

Product 1

HCID 112693693-Cyclobutyl-1-(2-pyridin-2-ylquinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

The mixture of 3-cyclobutyl-1-iodoimidazo[1,5-a]pyrazin-8-ylamine (62.8 mg 0.200 mmol), 2-pyridin-2-yl-7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline(79.1 mg, 1.2 eq.), Pd(PPh3)4 (14.0 mg, 6% eq.) and Na2CO3 (53.0 mg, 2.5 eq.) in DMF (5 ml)/H2O (1 ml) was flushed with N2 for 30 min at rt and heated at 80° C. for 16 h under N2. After that time, the reaction mixture was treated with H2O (20 ml), and was then extracted with CH2Cl2 (2×25 ml). The extracts were washed with H2O (2×20 ml), and dried over MgSO4. After the solid was filtered off and the solvent was removed in vacuo, the crude yellow oil (105 mg) was purified by MS directed purification system to obtain a yellow solid of 3-cyclobutyl-1-(2-pyridin-2-ylquinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine; 1H NMR (CDCl3, 400 MHz) δ 2.05-2.09 (m, 1 H), 2.15-2.22 (m, 1 H), 2.48-2.56 (m, 2 H), 2.62-2.72 (m, 2 H), 3.85 (quintet, 1 H, J=8.4 Hz), 5.27 (s, 2H), 7.09-7.10 (d, 1 H, J=4.8 Hz), 7.15-7.16 (d, 1 H, J=4.8 Hz), 7.36-7.39 (m, 1 H), 7.86-7.90 (m, 1 H), 7.97 (m, 2 H), 8.31-8.33 (d, 1 H, J=8.8 Hz), 8.43 (s, 1 H), 8.59-8.61 (d, 1 H, J=8.8 Hz), 8.67-8.69 (d, 1 H, J=7.6 Hz), 8.75-8.76 (d, 1 H, J=4.0 Hz); MS (ES+): 393.4 (M+1), tR(polar-5 min)=2.2 min.

Workup

  1. customwas flushed with N2 for 30 min at rt
  2. additionAfter that time, the reaction mixture was treated with H2O (20 ml)
  3. extractionwas then extracted with CH2Cl2 (2×25 ml)
  4. washThe extracts were washed with H2O (2×20 ml)
  5. dry with materialdried over MgSO4
  6. filtrationAfter the solid was filtered off
  7. customthe solvent was removed in vacuo
  8. customthe crude yellow oil (105 mg) was purified by MS
  9. custompurification system

Sources & evidence

ORD record
ord-b7a3d7f08eef4db3bba73a348198c384
Source dataset
uspto-grants-2013_02
Patent number
US08367826B2

Reaction notes

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