Potassium Phosphate, Tribasic → HCID 86703931, compound

HRID 1049934Notes

Reaction equation

[CH:1]1([NH:4][C:5]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12](I)[CH:13]=3)[N:8]=[CH:7][N:6]=2)[CH2:3][CH2:2]1.[Cl:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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.C1OCCOC1>[Cl:16][C:17]1[CH:22]=[C:21]([C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][CH:11]=2)[N:8]=[CH:7][N:6]=[C:5]3[NH:4][CH:1]2[CH2:3][CH2:2]2)[CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To an 8 mL screw-cap vial was added N-cyclopropyl-6-iodo-quinazolin-4-amine (0.25 mmol 78 mg), (3-chlorophenyl)boronic acid, (1.2 equiv., 0.30 mmol, 47 mg), 1-4 dioxane (0.6 mL), potassium phosphate tribasic, (2M in H2O, 3 equiv., 0.75 mmol, 0.0.38 mL), and Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(11) (0.05 equiv.; 0.013 mmol, 9 mg). The reaction was capped and shaken at 60° C. for 1 h. The reaction was cooled to room temperature and the phases separated. Organic phase was then concentrated. Crude was purified by reverse phase HPLC yielding 35 mg of product. 1H NMR (400 MHz, DMSO) δ 8.60-8.49 (m, 2H), 8.44-8.35 (s, 1H), 8.18-8.05 (d, J=8.7, 1H), 7.93-7.87 (s, 1H), 7.84-7.71 (m, 2H), 7.62-7.51 (t, J=7.9 Hz, 1H), 7.51-7.43 (d, J=8.4 Hz, 1H), 3.12-2.98 (m, 1H), 0.90-0.78 (m, 2H), 0.72-0.64 (m, 2H). LCMS M/Z (M+H)=296.

Workup

customTo an 8 mL screw-cap vial
customThe reaction was capped
temperatureThe reaction was cooled to room temperature
customthe phases separated
concentrationOrganic phase was then concentrated
customCrude was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-6ba2dc54910444249cb8991c9098227b
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382241B2

Reaction notes

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