Benzylamine → Benzyl-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine

HRID 1186511Notes

Reaction equation

HRID 1186511 reaction equation
CS([C:5]1[N:10]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)[C:14]3=[N:13][CH:12]=2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[CH2:27]([NH:34][C:5]1[N:10]=[C:9]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([N:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)[C:14]3=[N:13][CH:12]=2)[CH:8]=[CH:7][N:6]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

3

Reactant 2

HCID 7504BenzylamineHCID 682264863-(2-Methanesulfonyl-pyrimidin-4-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine

Product 1

HCID 66548628Benzyl-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amineYield 15.5%

Conditions

Temperature
140 °C

Procedure

The mixture of 3-(2-methanesulfonyl-pyrimidin-4-yl)-8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazine (from Example 46 supra) (150 mg, 0.402 mmol) and benzylamine (51.7 mg, 0.482 mmol) was heated at 140° C. with stirring for 2 hours. The resulting oil was purified by chromatography (silica gel, 10 g, 200˜300 mesh, eluting with dichloromethane:methanol, 30:1 to 10:1) to afford the crude product which was purified by prep-HPLC and concentrated to afford benzyl-{4-[8-(4-methyl-piperazin-1-yl)-imidazo[1,2-a]pyrazin-3-yl]-pyrimidin-2-yl}-amine (Yield 25 mg, 15.5%). 1H NMR (300 MHz, CDCl3): δ 8.71 (brs, 1H), 8.31 (d, 1H, J=4.8 Hz), 8.04 (s, 1H), 7.42-7.28 (m, 5H), 6.94 (d, 1H, J=5.4 Hz), 5.68 (brs, 1H), 4.71 (d, 2H, J=5.7 Hz), 4.24 (brs, 4H), 2.60-2.57 (m, 4 H), 2.36 (s, 3H). LC-MS: [M+H]+ 401.

Workup

  1. customThe resulting oil was purified by chromatography (silica gel, 10 g, 200˜300 mesh, eluting with dichloromethane:methanol, 30:1 to 10:1)
  2. customto afford the crude product which
  3. customwas purified by prep-HPLC and
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-387031ade7784ad7b1a9ffb2ef124a27
Source dataset
uspto-grants-2014_03
Patent number
US08673905B2

Reaction notes

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