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 390318노트

반응식

HRID 390318 반응식
[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

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 70297m-Chloroperbenzoic acid2회HCID 532553611-({3-[(1S,2S)-2-Hydroxycyclohexyl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)-4-pyridin-2-ylpiperidine-4-carbonitrile

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-a1da8810da9a4047aba6debdb0a265cb
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383638B2

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