Potassium Iodide → HCID 11718402, compound

HRID 1170476Notes

Reaction equation

HRID 1170476 reaction equation
[N:1]1([C:6]2[N:11]=[C:10]([CH3:12])[CH:9]=[C:8]([CH:13]3[CH2:17][CH2:16][CH2:15][NH:14]3)[N:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.Cl.[O:19]1[C:23]2[CH:24]=[CH:25][C:26]([CH2:28][N:29]([CH2:31][CH2:32]Cl)C)=[CH:27][C:22]=2[O:21][CH2:20]1.C(N(C(C)C)CC)(C)C.[I-].[K+]>CN(C=O)C>[O:19]1[C:23]2[CH:24]=[CH:25][C:26]([CH2:28][NH:29][CH2:31][CH2:32][N:14]3[CH2:15][CH2:16][CH2:17][CH:13]3[C:8]3[CH:9]=[C:10]([CH3:12])[N:11]=[C:6]([N:1]4[CH:5]=[CH:4][N:3]=[CH:2]4)[N:7]=3)=[CH:27][C:22]=2[O:21][CH2:20]1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 81531DiisopropylethylamineHCID 167502772-(1H-Imidazol-1-yl)-4-methyl-6-(pyrrolidin-2-yl)pyrimidineHCID 24777734HCID 24777734, compound

Product 1

HCID 11718402HCID 11718402, compoundYield 60.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of 2-imidazol-1-yl-4-methyl-6-pyrrolidin-2-yl-pyrimidine (2.1 g, 9.2 mmol) in DMF (15 mL) was added all at once to a stirred mixture of benzo[1,3]dioxol-5-ylmethyl-(2-chloro-ethyl)-methyl-amine hydrochloride salt (2.2 g, 8.1 mmol), DMF (10 mL) and diisopropylethylamine (2.5 mL) at ambient temperature under nitrogen. A catalytic amount of potassium iodide (340 mg, 2.0 mmol) is then added. The mixture is heated to 80° C. for 3 h. The solution is then cooled to room temperature, quenched into 200 mL of 1N dibasic potassium phosphate solution (pH 9), and extracted with ethyl acetate. The combined organics are dried over MgSO4, filtered and concentrated to a red residue. Purification via silica gel column chromatography (DCM to 4:1 DCM/MeOH) gave 2.0 g (52%) of benzo[1,3]dioxol-5-ylmethyl-{2-[2-(2-imidazol-1-yl-6-methyl-pyrimidin-4-yl)-pyrrolidin-1-yl]-ethyl}-amine as a red oil. [M+H]+ 421.30; 1H-NMR (400 MHz, CDCl3) δ 8.60 (s, 1H), 7.89 (s, 1H), 7.30 (s, 1H), 7.10 (s, 1H), 6.78 (s, 1H), 6.67 (m, 2 H), 5.88 (s, 2H), 3.52 (t, 1H, J=6.8 Hz), 3.6 (m, 3H), 2.77 (m, 1H), 2.2-2.6 (m, 8H), 1.62-1.95 (m, 3H). 13C-NMR (100 MHz, CDCl3) δ 175.7, 169.6, 154.0, 147.6, 146.5, 136.2, 132.8, 130.1, 121.9, 116.6, 115.0, 109.2, 107.8, 100.8, 69.8, 62.3, 56.0, 54.3, 53.1, 42.5, 33.2, 24.2, 23.4.

Workup

  1. temperatureThe solution is then cooled to room temperature
  2. customquenched into 200 mL of 1N dibasic potassium phosphate solution (pH 9)
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organics are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to a red residue
  7. customPurification via silica gel column chromatography (DCM to 4:1 DCM/MeOH)

Sources & evidence

ORD record
ord-d88b75eedba24f3ba5a0b65687923819
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

Loading…