Triethylamine → 1-(5-tert-Butyl-isoxazol-3-yl)-3-(4-{7-[4-(4-methyl-piperazine-1-carbonyl)-phenyl]-imidazo[1,2-a]pyridin-3-yl}-benzyl)-urea

HRID 1446771Notes

Reaction equation

HRID 1446771 reaction equation
Cl.Cl.[NH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]3[CH:16]=[CH:17][C:18]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([N:28]5[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]5)=[O:27])=[CH:22][CH:21]=4)=[CH:19][C:14]3=[N:13][CH:12]=2)=[CH:7][CH:6]=1.ClC(Cl)(Cl)C[O:38][C:39](=O)[NH:40][C:41]1[CH:45]=[C:44]([C:46]([CH3:49])([CH3:48])[CH3:47])[O:43][N:42]=1.C(N(CC)CC)C>CS(C)=O>[C:46]([C:44]1[O:43][N:42]=[C:41]([NH:40][C:39]([NH:3][CH2:4][C:5]2[CH:6]=[CH:7][C:8]([C:11]3[N:15]4[CH:16]=[CH:17][C:18]([C:20]5[CH:21]=[CH:22][C:23]([C:26]([N:28]6[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]6)=[O:27])=[CH:24][CH:25]=5)=[CH:19][C:14]4=[N:13][CH:12]=3)=[CH:9][CH:10]=2)=[O:38])[CH:45]=1)([CH3:49])([CH3:47])[CH3:48]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22768171HCID 22768171, compoundHCID 131727906{4-[3-(4-Aminomethyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-phenyl}-(4-methyl-piperazin-1-yl)-methanone, bis hydrochloride

Product 1

HCID 578634301-(5-tert-Butyl-isoxazol-3-yl)-3-(4-{7-[4-(4-methyl-piperazine-1-carbonyl)-phenyl]-imidazo[1,2-a]pyridin-3-yl}-benzyl)-ureaYield 15%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

Combine {4-[3-(4-aminomethyl-phenyl)-imidazo[1,2-a]pyridin-7-yl]-phenyl}-(4-methyl-piperazin-1-yl)-methanone, bis hydrochloride (0.30 g, 0.56 mmol), (5-tert-butyl-isoxazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (0.2 g, 0.63 mmol) and triethylamine (0.4 mL, 2.9 mmol) in DMSO (10 mL). Heat the mixture to 70° C., stir five hours, and cool to room temperature. Filter the solution through 10 g SCX column eluting with methanol→2 N ammonia in methanol. Concentrate fractions containing product to give a residue. Purify by chromatography (5% methanol in dichloromethane→10% methanol in dichloromethane→10% 2 N ammonia methanol in dichloromethane) to afford product (0.048 g, 15%). MS(ES), m/z 592 (M+1).

Workup

  1. temperaturecool to room temperature
  2. filtrationFilter the solution through 10 g SCX column
  3. washeluting with methanol→2 N ammonia in methanol
  4. additionConcentrate fractions containing product
  5. customto give a residue
  6. customPurify by chromatography (5% methanol in dichloromethane→10% methanol in dichloromethane→10% 2 N ammonia methanol in dichloromethane)

Sources & evidence

ORD record
ord-6d7c7a7e754a4040b1556d6e45a3a48b
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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