Potassium Carbonate → 4-(5-{3-[(4-Ethenylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one

HRID 1028121Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([CH:8]=[CH2:9])[CH:5]=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([C:18]2[S:22][C:21]([N:23]3[CH2:29][CH2:28][CH2:27][NH:26][C:25](=[O:30])[CH2:24]3)=[N:20][CH:19]=2)[CH:14]=[C:15]([CH3:17])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:8]([C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:10][C:11]2[CH:12]=[C:13]([C:18]3[S:22][C:21]([N:23]4[CH2:29][CH2:28][CH2:27][NH:26][C:25](=[O:30])[CH2:24]4)=[N:20][CH:19]=3)[CH:14]=[C:15]([CH3:17])[CH:16]=2)[N:7]=1)=[CH2:9]

Participants

Conditions

Temperature: 90 °C

Procedure

2-Chloro-4-ethenylpyrimidine (250 mg, 1.78 mmol), 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-diazepan-2-one (Intermediate XX, 538 mg, 1.78 mmol), potassium carbonate (490 mg, 3.56 mmol), Pd2(dba)3 (163 mg, 0.18 mmol), and XPhos (420 mg, 0.89 mmol) were added to an oven-dried vessel which was purged and flushed with argon. t-Amyl alcohol (5 ml) was added and the reaction mixture was heated at 90° C. for 18 h. The mixture was then cooled to room temperature, diluted with water and brine and extracted with ethyl acetate (3×). The organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The residual orange oil was purified via silica gel column chromatography (0-10% methanol/dichloromethane) to provide 188 mg of 4-(5-{3-[(4-ethenylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one as a yellow-orange solid. MS APCI: [M+H]+ m/z 407.1. 1H NMR (500 MHz, CDCl3) δ 8.37 (d, 1H, J=4.9 Hz), 7.77 (s, 1H), 7.50 (s, 1H), 7.42 (s, 1H), 7.24 (s, 1H), 6.89 (s, 1H), 6.68 (d, 1H, J=5.2 Hz), 6.67-6.46 (m, 2H), 5.65 (m, 1H, J=9.1 Hz), 4.26 (m, 2H), 3.85 (m, 2H), 3.32 (m, 2H), 2.33 (s, 3H), 1.99 (m, 2H). rhSyk=+++.

Workup

customwas purged
customflushed with argon
additiont-Amyl alcohol (5 ml) was added
temperatureThe mixture was then cooled to room temperature
additiondiluted with water and brine
extractionextracted with ethyl acetate (3×)
dry with materialThe organic layers were dried over magnesium sulfate
concentrationconcentrated under reduced pressure
customThe residual orange oil was purified via silica gel column chromatography (0-10% methanol/dichloromethane)

Sources & evidence

ORD record: ord-73948f6dce0c4fbba90d8c2dcc4f92c5
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08735417B2

Reaction notes

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