Benzenamine, 4-(4-morpholinyl)- → [5-(2-Dimethylamino-pyridin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)-amine

HRID 1921754Notes

Reaction equation

HRID 1921754 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]3[C:15]4[N:16]([CH:27]=[CH:28][N:29]=4)[C:17]([C:20]4[CH:25]=[CH:24][NH:23][C:22](=O)[CH:21]=4)=[CH:18][N:19]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.F[C:31]1C=C(B(O)O)C=[CH:33][N:32]=1.N1(C2C=CC(N)=CC=2)CCOCC1.CC([O-])(C)C.[Na+]>CN(C)C=O.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>[CH3:31][N:32]([CH3:33])[C:22]1[CH:21]=[C:20]([C:17]2[N:16]3[CH:27]=[CH:28][N:29]=[C:15]3[C:14]([NH:13][C:10]3[CH:11]=[CH:12][C:7]([N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)=[CH:8][CH:9]=3)=[N:19][CH:18]=2)[CH:25]=[CH:24][N:23]=1

Participants

7

Reactant 4

HCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 27833962-Fluoropyridine-4-boronic acidHCID 23676156Sodium t-butoxideHCID 248574474-[8-(4-Morpholin-4-yl-phenylamino)imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-one

Product 1

HCID 57399215[5-(2-Dimethylamino-pyridin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)-amine

Reagents, catalysts & solvents 2

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

Procedure

In the same way as described for Compound 85, step 1, using 2-fluoropyridine-4-boronic acid (0.047 g, 0.337 mmol), 5-bromo-imidazo[1,2-a]pyrazin-8-yl)-4-morpholin-4-yl-phenylamine (0.105 g, 0.281 mmol), Pd(PPh3)4 (32 mg, 0.0281 mmol) and NaOtBu (0.108 g, 1.12 mmol) in N,N-dimethylformamide/water (7 mL). The residue is chromatographed on silica gel, eluting with DCM followed by 95:5 DCM:NH3 (7M in MeOH), and the fractions containing the desired product are combined and evaporated to afford the title compound containing some side products. Additional purification by reverse phase prep HPLC affords the title compound as a yellow solid (18 mg, 16%). LCMS: Rt 1.99 min (98%), m/z (APCI) 416 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 3.09-3.13 (10H, m), 3.78 (4H, m), 6.89 (2H, m), 6.97 (2H, d), 7.59 (1H, s), 7.72 (1H, s), 7.93 (2H, d), 8.09 (1H, s), 8.12 (1H, d), 9.60 (1H, s).

Workup

  1. customThe residue is chromatographed on silica gel
  2. washeluting with DCM
  3. additionNH3 (7M in MeOH), and the fractions containing the desired product
  4. customevaporated

Sources & evidence

ORD record
ord-aafa8f6502d245d3b6524804e74f5bd2
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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