1,4-Dioxane → 2-{4-[4-(2-Hydroxyethylsulphonyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

HRID 1441316Notes

Reaction equation

HRID 1441316 reaction equation
[CH:1]([S:3]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:33]=[CH:32][C:15]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[N:27]([CH:28]([CH3:30])[CH3:29])[C:26]([CH3:31])=[N:25][CH:24]=4)[CH:20]=[CH:19][N:18]=3)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])=[CH2:2].[OH-].[Ba+2].[OH-].[O:37]1CCOCC1>O>[OH:37][CH2:2][CH2:1][S:3]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:33]=[CH:32][C:15]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[N:27]([CH:28]([CH3:29])[CH3:30])[C:26]([CH3:31])=[N:25][CH:24]=4)[CH:20]=[CH:19][N:18]=3)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:4])=[O:5]

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 6093286Barium hydroxideHCID 686838262-{4-[4-(Vinylsulphonyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

Product 1

HCID 686860822-{4-[4-(2-Hydroxyethylsulphonyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl)pyrimidine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2-{4-[4-(vinylsulphonyl)piperazin-1-yl]anilino}-4-(1-isopropyl-2-methyl-1H-imidazol-5-yl) pyrimidine (Example 29; 260 mg 0.56 mmol) and barium hydroxide (560 mg 3.27 mmol) in water (10 ml) was heated at 65° C.-90° C. over 6 hours. 1,4-dioxane (1 ml) was added after 1, 2, 3 and 5 hours. After evaporation under reduced pressure, the residue was treated with water (10 ml) and saturated sodium hydrogen carbonate solution (10 ml). The suspension was extracted with DCM (30 ml and 2×20 ml) and EtOAc (25 ml). Both extracts were washed (separately) with brine (10 ml) and dried (Na2SO4). The extracts were combined and evaporated. After chromatography on silica gel using MeOH:DCM (4:96 to 8:92), the title compound was obtained as a yellow solid (108 mg 40%). NMR: 1.40 (d, 6H), 2.49 (s, 3H), 3.13 (m, 4H), 3.23 (t, 2H), 3.30 (m, 4H), 3.76 (q, 2H), 5.01 (t, 1H), 5.69 (septuplet, 1H), 6.93 (d, 2H), 6.96 (d, 1H), 7.39 (s, 1H), 7.48 (d, 2H), 8.31 (d, 1H), 9.18 (s, 1H); m/z 486.

Workup

  1. temperaturewas heated at 65° C.-90° C. over 6 hours
  2. customAfter evaporation under reduced pressure
  3. additionthe residue was treated with water (10 ml) and saturated sodium hydrogen carbonate solution (10 ml)
  4. extractionThe suspension was extracted with DCM (30 ml and 2×20 ml) and EtOAc (25 ml)
  5. washBoth extracts were washed (separately) with brine (10 ml)
  6. dry with materialdried (Na2SO4)
  7. customevaporated

Sources & evidence

ORD record
ord-f6c6e6ac28da4af69606bb04cf08a677
Source dataset
uspto-grants-2010_02
Patent number
US07655652B2

Reaction notes

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