(2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one → 2-{4-[(2S5R)-4-Acetyl-2,5-dimethylpiperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-5-fluoropyrimidine

HRID 1441325Notes

Reaction equation

HRID 1441325 reaction equation
CN(C)/[CH:3]=[C:4](\[F:16])/[C:5]([C:7]1[N:11]([CH:12]([CH3:14])[CH3:13])[C:10]([CH3:15])=[N:9][CH:8]=1)=O.[C:18]([N:21]1[C@H:26]([CH3:27])[CH2:25][N:24]([C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([NH2:37])=[NH:36])=[CH:30][CH:29]=2)[C@@H:23]([CH3:38])[CH2:22]1)(=[O:20])[CH3:19]>>[C:18]([N:21]1[C@H:26]([CH3:27])[CH2:25][N:24]([C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]3[N:37]=[C:5]([C:7]4[N:11]([CH:12]([CH3:13])[CH3:14])[C:10]([CH3:15])=[N:9][CH:8]=4)[C:4]([F:16])=[CH:3][N:36]=3)=[CH:30][CH:29]=2)[C@@H:23]([CH3:38])[CH2:22]1)(=[O:20])[CH3:19]

Participants

3

Reactant 2

HCID 58127046(2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-oneHCID 178473863HCID 178473863, compound

Product 1

HCID 686870142-{4-[(2S5R)-4-Acetyl-2,5-dimethylpiperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-5-fluoropyrimidine

Procedure

The title compound was prepared from (2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one (Method 14; 335 mg, 1.40 mmol) and N-[4-((2S,5R)-4-acetyl-2,5-dimethylpiperazin-1-yl)phenyl]guanidine (Method 35; 737.1 mg, 2.10 mmol) by the procedure of Example 116. The reaction mixture was evaporated under reduced pressure and the residue purified by chromatography on silica gel with MeOH:DCM:EtOAc (1:49.5:49.5 to 6:47:47) to give a solid which required further purification with MeOH:DCM (1:99 to 6:94). After trituration with ether and evaporation of the solvent, the title compound was obtained as a solid which was dried in vac oven overnight at 50° C. (330 mg, 51%). NMR: (500 MHz) 0.95 (d, 3H), 1.33 (d, 3H), 1.40 (d, 6H), 2.03 (s, 3H), 2.50 (s, 3H+DMSO), 3.17 (m, 2H), 3.43 (brs, 1H), 3.83 (brs, 1H), 4.00 (m, 1H), 4.47 (brs, 1H), 5.40 (septet, 1H), 6.83 (d, 2H), 7.32 (d, 1H), 7.37 (d, 2H), 8.35 (d, 1H), 8.7 (s, 1H); 19F NMR (500 MHz MHz) −149.95 (t, 1F); m/z 466.

Workup

  1. customThe reaction mixture was evaporated under reduced pressure
  2. customthe residue purified by chromatography on silica gel with MeOH:DCM:EtOAc (1:49.5:49.5 to 6:47:47)
  3. customto give a solid which required
  4. customfurther purification with MeOH:DCM (1:99 to 6:94)
  5. customAfter trituration with ether and evaporation of the solvent

Sources & evidence

ORD record
ord-d06417a44d96459c94566fc75f9087d3
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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