Diglyme → 6-(2-Fluoro-4-nitrophenoxy)-N-(4-methoxybenzyl)pyrimidin-4-amine

HRID 1670201Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13](Cl)[N:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1.[F:18][C:19]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:20]=1[OH:28].CCN(C(C)C)C(C)C.COCCOCCOC>CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][NH:8][C:9]2[CH:14]=[C:13]([O:28][C:20]3[CH:21]=[CH:22][C:23]([N+:25]([O-:27])=[O:26])=[CH:24][C:19]=3[F:18])[N:12]=[CH:11][N:10]=2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of N-(4-methoxybenzyl)-6-chloropyrimidin-4-amine (2.3 g, 9.2 mmol), 2-fluoro-4-nitrophenol (1.45 g, 9.2 mmol), DIPEA (15 mL), and 2-methoxyethyl ether (75 mL) was heated at 160° C. in a sealed pressure bottle for 50 h. The mixture was cooled, poured onto crushed ice (200 g), treated with EtOAc (200 mL). After vigorously stirring for 10 min, the insoluble material was filtered off. The EtOAc phase was washed with saturated aq. Na2CO3 solution (100 mL), brine (3×100 mL), dried (MgSO4) and concentrated in vacuo. The gummy solid obtained was triturated with isopropyl ether to give the title compound (1.75 g, 76%) as a brown solid. 1H NMR (DMSO-d6) δ 8.32 (dd, 1H, J=10.2, 2.0 Hz), 8.15 (d, 2H, J=9.2 Hz), 8.05 (br s, 1H), 7.61 (dd, 1H, J=8.4, 8.4 Hz), 7.26 (d, 2H, J=8.5 Hz), 6.91 (d, 2H, J=8.5 Hz), 6.14 (br s, 1H), 4.48 (br s, 2H), 3.74 (s, 3H).

Workup

temperatureThe mixture was cooled
additionpoured
filtrationthe insoluble material was filtered off
washThe EtOAc phase was washed with saturated aq. Na2CO3 solution (100 mL), brine (3×100 mL)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe gummy solid obtained
customwas triturated with isopropyl ether

Sources & evidence

ORD record: ord-76156b78f019425687d74faf0b5a72eb
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989477B2

Reaction notes

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