Ammonia → [5-(2-Amino-pyridin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine

HRID 1366140Notes

Reaction equation

F[C:2]1[CH:7]=[C:6]([C:8]2[N:13]3[CH:14]=[CH:15][N:16]=[C:12]3[C:11]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)=[CH:20][CH:19]=3)=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[NH3:31]>CO.O1CCOCC1>[NH2:31][C:2]1[CH:7]=[C:6]([C:8]2[N:13]3[CH:14]=[CH:15][N:16]=[C:12]3[C:11]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)=[CH:20][CH:19]=3)=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of [5-(2-fluoro-pyridin-4-yl)-imidazo[1,2-a]pyrazin-8-yl]-[4-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.0272, 0.067 mmol) (from Example 125) in a mixture of aq. NH3 (2.5 mL):1M NH3 in MeOH (2.5 mL) is stirred at 100° C. overnight. Additional aq. NE3 (5 mL) and 0.5M NH3 in dioxane (2 mL) are added and the mixture stirred at 120° C. for 4 days. The mixture is concentrated in vacuo and purified by reverse phase HPLC affording the title compound (4.2 mg, 16%). LCMS: Rt 3.76 min (95%) m/z (APCI) 401 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm). 2.26 (3H, s), 2.49-2.53 (4H, t), 3.12-3.15 (4H, m), 6.18 (2H, br s) 6.76 (1H, s), 6.81 (1H, d), 6.97 (2H, d), 7.51 (1H, s), 7.72 (1H, s), 7.88 (2H, d), 8.04 (1H, s), 8.09 (1H, d), 9.55 (1H, s).

Workup

concentrationThe mixture is concentrated in vacuo
custompurified by reverse phase HPLC

Sources & evidence

ORD record: ord-c419a2ce26c540d4a97aade94006be6c
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07893058B2

Reaction notes

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