2-Fluoro-4-nitrophenol → 4-(2-Fluoro-4-nitrophenoxy)-N-(2-morpholinoethyl)thieno[3,2-d]pyrimidine-6-carboxamide

HRID 1710895Notes

Reaction equation

Cl[C:2]1[C:3]2[S:10][C:9]([C:11]([NH:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[OH:32].C([O-])([O-])=O.[K+].[K+].CO.C(Cl)Cl>O(C1C=CC=CC=1)C1C=CC=CC=1>[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[O:32][C:2]1[C:3]2[S:10][C:9]([C:11]([NH:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a stirred solution of compound 23 (458 mg, 1.40 mmol) in Ph2O (6 mL) was added 2-fluoro-4-nitrophenol (242 mg, 1.54 mmol). The reaction mixture was heated at 120° C. for 2.5 hours, treated with K2CO3 (80 mg, 0.56 mmol) and heated at the same temperature for additional 18 hours. After cooling, the reaction mixture was purified by flash chromatography on a silica gel column (eluents EtOAc-hexane 5:95, 1:1, then MeOH-DCM, 5:95 and 1:9), to afford the title compound 24 (570 mg, 91% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ(ppm): 9.09 (t, J=5.6 Hz, 1H), 8.77 (s, 1H), 8.41 (dd, J=2.4 and 10.4 Hz, 1H), 8.30 (s, 1H), 8.22 (dd, J=2.4 and 8.8 Hz, 1H), 7.88 (t, J=8.8 Hz, 1H), 3.60-3.52 (m, 4H), 3.45 (q, J=6.8 Hz, 2H), 2.50 (q, J=6.8 Hz, 2H), 2.46-2.40 (m, 4H).

Workup

temperatureheated at the same temperature for additional 18 hours
temperatureAfter cooling
customthe reaction mixture was purified by flash chromatography on a silica gel column (eluents EtOAc-hexane 5:95, 1:1

Sources & evidence

ORD record: ord-971654aae2f344439f4f38dece7fd513
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07790729B2

Reaction notes

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