Hydrochloric Acid → 1-({3-[(1S,2S)-2-Hydroxycyclohexyl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile 1-oxide

HRID 390318Notes

Reaction equation

HRID 390318 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]3[CH:37]=[CH:36][CH:35]=[CH:34][C:13]3=[C:14]([CH2:19][N:20]3[CH2:25][CH2:24][C:23]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)([C:26]#[N:27])[CH2:22][CH2:21]3)[CH:15]=2)[N:10]=[CH:9]1.Cl.ClC1C=C(C=CC=1)C(OO)=[O:44].C(#N)C>C1COCC1.O>[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[N:8]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]3[CH:37]=[CH:36][CH:35]=[CH:34][C:13]3=[C:14]([CH2:19][N+:20]3([O-:44])[CH2:25][CH2:24][C:23]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)([C:26]#[N:27])[CH2:22][CH2:21]3)[CH:15]=2)[N:10]=[CH:9]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 70297m-Chloroperbenzoic acid2×HCID 532553611-({3-[(1S,2S)-2-Hydroxycyclohexyl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile

Product 1

HCID 533037641-({3-[(1S,2S)-2-Hydroxycyclohexyl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile 1-oxide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution 1-({3-[(1S,2S)-2-hydroxycyclohexyl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile (Example 2, 9.0 mg, 0.018 mmol) in 1.5 mL of THF and 0.018 mL HCl (1 M in dioxane, 0.18 mL, 0.18 mmol) was added m-chloroperoxybenzoic acid (3.2 mg, 0.18 mmol). After 1 h, acetonitrile (1 mL) was added. After 15 h, additional m-chloroperbenzoic acid (1.6 mg, 0.090 mmol) was added. After 30 min, the reaction was treated with water and extracted 3× with ethyl acetate. The combined organic solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified via preparative TLC eluting with 10% methanol in dichloromethane to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 510.2505 for [M+H]+ [Cal'd for C30H32N5O3, [M+H]+=510.2500]: 1H NMR (400 MHz, CDCl3) δ 9.05 (d, J=8.4 Hz, 1H), 8.61 (d, J=4.9 Hz, 1H), 8.54 (d, J=8.5 Hz, 1H), 8.46 (s, 1H), 8.38 (s, 1H), 8.06 (s, 1H), 7.95-7.92 (m, 1H), 7.84 (t, J=7.8 Hz, 1H), 7.75-7.71 (m, 2H), 7.47 (d, J=8.0 Hz, 1H), 4.65 (br s, 1H), 4.05 (br s, 1H), 3.95-3.85 (m, 2H), 3.84-3.82 (m, 2H), 3.68-3.49 (m, 1H), 3.21-3.14 (m, 1H), 2.26-1.71 (m, 6H), 1.68-0.83 (m, 6H).

Workup

  1. waitAfter 15 h
  2. waitAfter 30 min
  3. extractionextracted 3× with ethyl acetate
  4. dry with materialThe combined organic solution was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified via preparative TLC
  8. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-a1da8810da9a4047aba6debdb0a265cb
Source dataset
uspto-grants-2013_02
Patent number
US08383638B2

Reaction notes

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