Cyclohexanol → HCID 59993331, compound

HRID 238221Notes

Reaction equation

HRID 238221 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[NH:28][C:27](=[O:29])[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)[CH2:14][CH2:13]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[CH:30]1(O)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>O=P(Cl)(Cl)Cl>[CH:30]1([O:29][C:27]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=[C:19]([CH2:18][N:15]3[CH2:14][CH2:13][N:12]([S:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)(=[O:10])=[O:11])[CH2:17][CH2:16]3)[N:28]=2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 7966CyclohexanolHCID 135808011HCID 135808011, compound

Product 1

HCID 59993331HCID 59993331, compound

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

2-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-ylmethyl]-3H-quinazolin-4-one (83 mg, 0.2 mmol) in POCl3 (1 mL) was heated to 90° C. for 2 hours. Then the excess POCl3 was removed in vacuo. The residue was dissolved in toluene (5 mL) and then the solvent was removed in vacuo. This step was repeated twice more. The residue was then dissolved in THF (1 mL) and cyclohexanol (211 μL, 2 mmol) was added. The reaction was stirred at room temperature for 1 day. The reaction mixture was partitioned between dichloromethane and water. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by HPLC (in the absence of TFA). 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J=7.5 Hz, 1H), 7.89 (d, J=8.3 Hz, 1H), 7.79 (t, J=7.3 Hz, 1H), 7.72 (dt, J=9.5, 2.4 Hz, 2H), 7.52 (t, J=7.4 Hz, 1H), 7.01 (dt, J=9.5, 2.4 Hz, 2H), 5.39 (quintet, J=4.2 Hz, 1H), 3.90 (m, 5H), 3.16 (m, 4H), 2.90 (m, 4H), 1.66 (m, 10H); HPLC ret. time 2.93 min, 10-99% CH3CN, 5 min run; ESI-MS m/z 497.3 (M+1)+.

Workup

  1. customThen the excess POCl3 was removed in vacuo
  2. dissolutionThe residue was dissolved in toluene (5 mL)
  3. customthe solvent was removed in vacuo
  4. dissolutionThe residue was then dissolved in THF (1 mL)
  5. customThe reaction mixture was partitioned between dichloromethane and water
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by HPLC (in the absence of TFA)
  9. customHPLC ret. time 2.93 min, 10-99% CH3CN, 5 min

Sources & evidence

ORD record
ord-3405826e2f8346419e9d96b09a51e8f8
Source dataset
uspto-grants-2014_02
Patent number
US08642609B2

Reaction notes

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