Phosphorus oxychloride → HCID 59380503, compound

HRID 2353823Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]1[CH:19]=[CH:18][C:9]2[C:10]3[C:15](=O)[NH:14][CH:13]=[N:12][C:11]=3[S:17][C:8]=2[CH:7]=1)[CH3:2].C(N(C(C)C)CC)(C)C.P(Cl)(Cl)([Cl:32])=O>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]1[CH:19]=[CH:18][C:9]2[C:10]3[C:15]([Cl:32])=[N:14][CH:13]=[N:12][C:11]=3[S:17][C:8]=2[CH:7]=1)[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (4-oxo-3,4-dihydro-benzo[4,5]thieno[2,3-d]pyrimidin-7-yl)-acetic acid ethyl ester (1.78 g, 6.17 mmol, 1 equiv, from step 3) in toluene (15 mL) were added diisopropylethylamine (1.18 mL, 6.79 mmol, 1.1 equiv) and phosphorous oxychloride (0.63 mL, 6.79 mmol, 1.1 equiv) at 0° C. under argon. The flask was equipped with a reflux condenser and heated at 80° C. for 5 h. The reaction mixture was cooled to rt and quenched with ice/saturated aqueous NaHCO3. The resulting mixture was extracted with EtOAc (3×80 mL). The combined organic layers was dried over sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography (20% EtOAc/hexane) to yield 1.12 g (3.6 mmol, 56%) of a light yellow solid. 1H-NMR (DMSO-d6) δ 9.01 (s, 1H), 8.64 (d, J=8.6 Hz, 1H), 8.15 (s, 1H), 7.61 (d, J=8.6 Hz, 1H), 4.10 (q, 2H), 3.92 (s, 2H), 1.20 (t, 3H), LCMS RT=3.19 min, [M+H]+=307

Workup

customThe flask was equipped with a reflux condenser
temperatureThe reaction mixture was cooled to rt
customquenched with ice/saturated aqueous NaHCO3
extractionThe resulting mixture was extracted with EtOAc (3×80 mL)
dry with materialThe combined organic layers was dried over sodium sulfate
concentrationconcentrated in vacuo
customThe crude material was purified by flash chromatography (20% EtOAc/hexane)

Sources & evidence

ORD record: ord-de2ae4da16fa46b89272264a0165562d
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07750017B2

Reaction notes

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