2-Chloro-6-(cyclopentyloxy)-7-methoxyquinazoline → HCID 178486848, compound

HRID 1672492Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([O:18][CH3:19])=[C:7]([O:12][CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[CH:8]=2)[N:3]=1.[NH2:20][C@H:21]1[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23][CH2:22]1>CC#N>[CH:13]1([O:12][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][C:6]=2[O:18][CH3:19])[N:3]=[C:2]([NH:20][C@H:21]2[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23][CH2:22]2)[N:11]=[CH:10]3)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a suspension of 2-chloro-6-(cyclopentyloxy)-7-methoxyquinazoline (100.0 mg, 0.36 mmol) (obtained from the company compound collection) in 20 ml of CH3CN at room temperature was added the trans-4-aminocyclohexanol (207.0 mg, 1.79 mmol). The resulting mixture was heated to 60° C. for 5 hours. The reaction was cooled and partitioned with EA and water. The organics layer was washed with water (2×20 mL) and brine (20 mL), combined and dried over MgSO4, Removal of the solvent provided a yellow solid. The crude material was purified using silica gel eluting with 95/5 EA/MeOH to afford 45.9 mg of the desired product with 35.9% yield. 1H NMR (400 MHz, DMSO-d6) ppm 1.14-1.40 (m, 4H), 1.51-2.06 (m, 12H), 3.36-3.52 (m, 1H), 3.66-3.80 (m, 1H), 3.82-3.95 (m, 3H), 4.54 (s, 1H), 4.75-4.88 (m, 1H), 6.74 (d, J=8.06 Hz, 1H), 6.83 (s, 1H), 7.12 (s, 1H), 8.80 (s, 1H). HRMS: m/z 358.21218 [M+H]+), calc. 358.21252. MS m/z, (APCI); 358.2 ([M+H]+).

Workup

temperatureThe reaction was cooled
custompartitioned with EA and water
washThe organics layer was washed with water (2×20 mL) and brine (20 mL)
dry with materialdried over MgSO4, Removal of the solvent
customprovided a yellow solid
customThe crude material was purified

Sources & evidence

ORD record: ord-eda2b931489c481bac55b74ffe4b8ea6
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07998978B2

Reaction notes

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