Dimethylamine → Imatinib

HRID 273298Notes

Reaction equation

HRID 273298 reaction equation
[NH:1]([C:5]1[CH:6]=[C:7]([NH:12][C:13](=[O:28])[C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)=[CH:16][CH:15]=2)[CH:8]=[CH:9][C:10]=1[CH3:11])[C:2]([NH2:4])=[NH:3].[CH3:29][NH:30][CH3:31]>C(O)CCC>[CH3:27][N:24]1[CH2:25][CH2:26][N:21]([CH2:20][C:17]2[CH:16]=[CH:15][C:14]([C:13]([NH:12][C:7]3[CH:8]=[CH:9][C:10]([CH3:11])=[C:5]([NH:1][C:2]4[N:4]=[C:5]([C:10]5[CH:29]=[N:30][CH:31]=[CH:8][CH:9]=5)[CH:6]=[CH:7][N:3]=4)[CH:6]=3)=[O:28])=[CH:19][CH:18]=2)[CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 674DimethylamineHCID 178426565HCID 178426565, compound

Product 1

HCID 5291Imatinib

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
150 °C

Procedure

A suspension of N-(3-guanidino-4-methyl-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide (30 g, 79 mmol) in n-butanol (150 ml) at 120° C. under an atmosphere of nitrogen is treated with 3-dimethylamino-1-pyridin-3-yl-propenone (15.3 g, 87 mmol). The resulting suspension is heated at 150° C. for 5 hrs. The reaction mixtures becomes a homogeneous deep orange solution and dimethylamine is removed by the distillation of n-butanol (130 ml). n-Butanol (20 ml) is added during the distillation. Butyl acetate (60 ml) is added dropwise at 100° C. and the solution is cooled to 0° C. within 1 hr and stirred at 0° C. for 16 hrs. The resulting deep orange suspension is filtered off with suction, the isolated solid is washed with n-butanol (2×50 ml) and water (2×50 ml) and dried in vacuo at 60° C. Yield: 36.4 g of the title compound, 93% based on theory, as off-whitecrystals. (99.6% area by HPLC).

Workup

  1. customis removed by the distillation of n-butanol (130 ml)
  2. additionn-Butanol (20 ml) is added during the distillation
  3. additionButyl acetate (60 ml) is added dropwise at 100° C.
  4. temperaturethe solution is cooled to 0° C. within 1 hr
  5. filtrationThe resulting deep orange suspension is filtered off with suction
  6. washthe isolated solid is washed with n-butanol (2×50 ml) and water (2×50 ml)
  7. customdried in vacuo at 60° C

Sources & evidence

ORD record
ord-c475e92afd2742a6aa168ad5125ffb1b
Source dataset
uspto-grants-2008_11
Patent number
US07456283B2

Reaction notes

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