2-Hydroxyisobutyric acid → 2-{4-[4-(2-Hydroxy-2-methylpropionyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-5-chloropyrimidine

HRID 1441319Notes

Reaction equation

HRID 1441319 reaction equation
[OH:1][C:2]([CH3:7])([CH3:6])[C:3](O)=[O:4].C(N1C=CN=C1)(N1C=CN=C1)=O.[N:20]1([C:26]2[CH:48]=[CH:47][C:29]([NH:30][C:31]3[N:36]=[C:35]([C:37]4[N:41]([CH:42]([CH3:44])[CH3:43])[C:40]([CH3:45])=[N:39][CH:38]=4)[C:34]([Cl:46])=[CH:33][N:32]=3)=[CH:28][CH:27]=2)[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1>C(Cl)Cl>[OH:1][C:2]([CH3:7])([CH3:6])[C:3]([N:23]1[CH2:24][CH2:25][N:20]([C:26]2[CH:27]=[CH:28][C:29]([NH:30][C:31]3[N:36]=[C:35]([C:37]4[N:41]([CH:42]([CH3:44])[CH3:43])[C:40]([CH3:45])=[N:39][CH:38]=4)[C:34]([Cl:46])=[CH:33][N:32]=3)=[CH:47][CH:48]=2)[CH2:21][CH2:22]1)=[O:4]

Participants

5

Reactant 3

HCID 116712-Hydroxyisobutyric acidHCID 682631,1'-CarbonyldiimidazoleHCID 686895762-[4-(piperazin-1-yl)anilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-5-chloropyrimidine

Product 1

HCID 686886072-{4-[4-(2-Hydroxy-2-methylpropionyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-5-chloropyrimidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

2-Hydroxyisobutyric acid (162 mg. 1 mmol) was added to a solution of 1,1′-carbonyldiimidazole (162 mg. 1 mmol) in DCM (4 ml) and stirred at room temperature for 15 minutes. A solution of 2-[4-(piperazin-1-yl)anilino]-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)-5-chloropyrimidine (Example 34. 400 mg. 0.97 mmol) in DCM (8 ml) was added and stirring continued for 19 hours. DCM (25 ml) was added and the organic layer was washed with 5% (v/v) acetic acid (15 ml), water (15 ml), brine (15 ml) and dried before evaporating under reduced pressure. Chromatography on silica gel with MeOH:DCM (4:96 to 8:92) gave the title compound, after ether trituration, as a solid. (67 mg 14%). NMR: (500 MHz) 1.30 (d, 6H), 1.34 (d, 6H), 2.48 (s, 3H), 3.04 (t, 4H), 3.62 (b s, 4H), 4.00 (b s, 4H), 4.79 (septuplet, 1H), 5.41 (s, 1H), 6.90 (d, 2H), 7.22 (s, 1H), 7.48 (d, 2H), 8.51 (s, 1H), 9.49 (s, 1H); m/z 498.

Workup

  1. stirringstirring
  2. waitcontinued for 19 hours
  3. washthe organic layer was washed with 5% (v/v) acetic acid (15 ml), water (15 ml), brine (15 ml)
  4. customdried
  5. custombefore evaporating under reduced pressure

Sources & evidence

ORD record
ord-123e26babaa3436aac17aa9f7ee05db5
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

Loading…