Triethylamine → HCID 86666962, compound

HRID 82459Notes

Reaction equation

HRID 82459 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])[CH:5]=[CH:4][N:3]=1.OO.NC(N)=[O:35].C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[CH:10]=[C:11]3[C:16](=[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=24)[N:15]=[CH:14][N:13]([C@H:23]2[CH2:28][CH2:27][O:26][CH2:25][C@@H:24]2[OH:29])[C:12]3=[O:30])[CH:5]=[CH:4][N+:3]=1[O-:35]

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 9845Trifluoroacetic anhydride2×HCID 10340Sodium CarbonateHCID 31294Carbamide Peroxide2×HCID 510008646-[(2-chloropyridin-4-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

Product 1

HCID 86666962HCID 86666962, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-[(2-chloropyridin-4-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 15, 54.5 mg, 0.129 mmol) in 2 mL of dichloromethane was added urea hydrogen peroxide (60.8 mg, 0.646 mmol), triethylamine (0.090 mL, 0.65 mmol), and trifluoroacetic anhydride (0.036 mL, 0.26 mmol). After 30 min, additional urea hydrogen peroxide (36.5 mg, 0.388 mmol), and triethylamine (0.18 mL, 1.3 mmol), and trifluoroacetic anhydride (0.146 mL, 1.03 mmol) were added. After 3 h, the reaction was cooled to −78° C., treated with 10% aqueous sodium carbonate, and extracted 3× with dichloromethane. The combined organic solutions were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was suspended in methanol, and the slurry was filtered and washed with additional methanol to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 438.1214 for [M+H]+ [Calc'd for C23H21ClN3O4, [M+H]+=438.1215]: 1H NMR (400 MHz, d6-DMSO) δ 9.01 (d, J=1.1 Hz, 1H), 8.73 (s, 1H), 8.32 (d, J=6.8 Hz, 1H), 8.14 (d, J=7.7 Hz, 1H), 8.06 (s, 1H), 7.82-7.74 (m, 3H), 7.22-7.20 (m, 1H), 5.31 (d, J=5.5 Hz, 1H), 4.67 (br s, 1H), 4.56 (s, 2H), 4.18 (br s, 1H), 4.00-3.93 (m, 2H), 3.46 (t, J=11.0 Hz, 1H), 3.15 (t, J=10.5 Hz, 1H), 2.24 (br s, 1H), 1.92-1.90 (m, 1H).

Workup

  1. waitAfter 3 h
  2. extractionextracted 3× with dichloromethane
  3. dry with materialThe combined organic solutions were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. filtrationthe slurry was filtered
  7. washwashed with additional methanol

Sources & evidence

ORD record
ord-450f07156af74821aa8591b2989d8a30
Source dataset
uspto-grants-2014_09
Patent number
US08846702B2

Reaction notes

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