Dimethylformamide dimethyl acetal → HCID 10434757, compound

HRID 639413Notes

Reaction equation

HRID 639413 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[C:24]([C:28]5[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=5)=[N:25][NH:26][CH:27]=4)[CH:20]=[CH:19][N:18]=3)=[CH:12][CH:11]=2)[CH2:5][CH2:4]1)[CH3:2].[CH3:35]N(C(OC)OC)C>C1(C)C=CC=CC=1>[CH2:1]([N:3]1[CH2:4][CH2:5][N:6]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[C:24]([C:28]5[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=5)=[N:25][N:26]([CH3:35])[CH:27]=4)[CH:20]=[CH:19][N:18]=3)=[CH:14][CH:15]=2)[CH2:7][CH2:8]1)[CH3:2]

Participants

4

Reactant 2

HCID 78373Dimethylformamide dimethyl acetal2×HCID 178462734HCID 178462734, compound

Product 1

HCID 10434757HCID 10434757, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

[4-(4-Ethyl-piperazin-1-ylmethyl)-phenyl]-[4-(3-p-tolyl-1H-pyrazol-4-yl)-pyrimidin-2-yl]-amine (Example 101) (165 mg; 0.364 mMol) is suspendend in toluene (3 mL) and treated with DMF-DMA (168 mg; 1.32 mMol, 187 μL) at rt. The mixture is stirred at reflux for a total of 102 h whereby additional DMF-DMA is added after 48 h (187 μL), after 61 h (187 μL) and after 82 h (374 μL). Upon completion of the reaction and cooling to rt the solvent is removed under reduced pressure. The crude product mixture is purified by reversed phase chromatography (Lichroprep® RP18 15-25 μM; eluting with 18% CH3CN (0.1% TFA)/82% H2O (0.1% TFA)). The pure fractions 27-34 are combined and evaporated. The residue is dissolved in H2O (2 mL) and neutralized with 1N NaOH. The crystalline product (free base) is filtered off, washed with H2O and dried at 60° C. to obtain the title compound as beige crystalline powder.

Workup

  1. additionis added after 48 h (187 μL)
  2. waitafter 82 h (374 μL)
  3. customUpon completion of the reaction
  4. customis removed under reduced pressure
  5. customThe crude product mixture is purified by reversed phase chromatography (Lichroprep® RP18 15-25 μM; eluting with 18% CH3CN (0.1% TFA)/82% H2O (0.1% TFA))
  6. customevaporated
  7. dissolutionThe residue is dissolved in H2O (2 mL)
  8. filtrationThe crystalline product (free base) is filtered off
  9. washwashed with H2O
  10. customdried at 60° C.

Sources & evidence

ORD record
ord-66dca97173474727945df72f03c98c7b
Source dataset
uspto-grants-2010_04
Patent number
US07691855B2

Reaction notes

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