1,4-Dioxane → HCID 86703936, compound

HRID 1049939Notes

Reaction equation

[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:13]#[N:14])[CH:8]=[C:9](Cl)[CH:10]=2)[N:5]=[CH:4][N:3]=1.[F:15][C:16]1[CH:17]=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C(OCC)(=O)C.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[NH2:1][C:2]1[C:11]2[C:6](=[C:7]([C:13]#[N:14])[CH:8]=[C:9]([C:20]3[CH:19]=[CH:18][CH:17]=[C:16]([F:15])[CH:21]=3)[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To an 8 mL vial was added 4-amino-6-chloro-quinazoline-8-carbonitrile (100 mg, 0.49 mmol) followed by (3-fluorophenyl)boronic acid (2 equiv., 1.0 mmol, 0.13676 g), potassium phosphate tribasic (2M in water, 4 equiv., 2.0 mmol, 1 mL), Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.05 equiv., 0.024 mmol, 17 mg) and dioxane (2 mL). The reaction was capped and shaken at 100° C. for 2 h. The reaction was cooled to room temperature, then diluted with 4 mL ethyl acetate and 3 mL water. The resulting precipitate was collected by filtration, yielding 72 mg of desired product. 1H NMR (400 MHz, DMSO) δ 8.94-8.89 (d, J=1.5 Hz, 1H), 8.77-8.72 (d, J=1.4 Hz, 1H), 8.55-8.50 (s, 1H), 8.43-8.13 (s, 2H), 7.83-7.74 (t, J=8.5 Hz, 2H), 7.63-7.55 (dd, J=14.5, 8.0 Hz, 1H), 7.33-7.25 (dd, J=12.5, 4.5 Hz, 1H). LCMS M/Z (M+H)=265.

Workup

customThe reaction was capped
temperatureThe reaction was cooled to room temperature
filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record: ord-b8e787192218422c9b51fea6db9a7257
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382241B2

Reaction notes

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