(2-(2-Fluorophenyl)-1H-imidazol-5-yl)methanol → HCID 59337790, compound

HRID 12450Notes

Reaction equation

HRID 12450 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:9][C:10]([CH2:13]O)=[CH:11][N:12]=1.[CH:15]([N:18]1[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)([CH3:17])[CH3:16]>O=S(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:9][C:10]([CH2:13][N:21]2[CH2:22][CH2:23][CH2:24][N:18]([CH:15]([CH3:17])[CH3:16])[CH2:19][CH2:20]2)=[CH:11][N:12]=1

Participants

4

Reactant 2

HCID 9990132(2-(2-Fluorophenyl)-1H-imidazol-5-yl)methanolHCID 122365131-(Propan-2-yl)-1,4-diazepane

Product 1

HCID 59337790HCID 59337790, compound

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
65 °C

Procedure

[2-(2-Fluorophenyl)-1H-imidazol-5-yl]methyl alcohol (69 mg, 0.36 mmol, prepared essentially as described in PCT International Publication No. WO 96/16040) is dissolved in SOCl2 (4 mL) and stirred at 65° C. for 1 hr. The reaction mixture is cooled to rt then concentrated in vacuo. The residue is dissolved in toluene, and then re-concentrated. The residue is suspended in CHCl3 (3 mL) at it Et3N (1 mL) is added, followed by 4-isopropyl-1,4-diazepane (0.8 mL, 0.4 mmol). The reaction mixture is stirred for 90 min at rt, and then the solvent is removed in vacuo. The residue is dissolved in CH2Cl2 and applied to a PTLC plate then eluted with EtOAc/MeOH/Et3N (10/2/1). The product is removed from the plate and the silica stirred in EtOAc/MeOH (10/1) then filtered. The filtrate is concentrated to give the title compound. 1H NMR 8.24 (br t, 1H), 7.30-7.21 (m, 2H), 7.13 (dd, 1H), 7.01 (s, 1H), 3.70 (s, 2H), 2.90 (m, 1H), 2.74-2.71 (m, 8H), 1.80 (br s, 2H), 1.06 (d, 3H), 1.02 (d, 3H).

Workup

  1. temperatureThe reaction mixture is cooled to rt
  2. concentrationthen concentrated in vacuo
  3. dissolutionThe residue is dissolved in toluene
  4. concentrationre-concentrated
  5. additionis added
  6. stirringThe reaction mixture is stirred for 90 min at rt
  7. customthe solvent is removed in vacuo
  8. dissolutionThe residue is dissolved in CH2Cl2
  9. washthen eluted with EtOAc/MeOH/Et3N (10/2/1)
  10. customThe product is removed from the plate
  11. stirringthe silica stirred in EtOAc/MeOH (10/1)
  12. filtrationthen filtered
  13. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-8b22fd99aea743d896a2430827fb4c7c
Source dataset
uspto-grants-2010_06
Patent number
US07728009B1

Reaction notes

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