Diglyme → N-(4-(6-(4-(benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)acetamide

HRID 1670236Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([NH:24][C:25](=[O:37])[CH2:26]C(NC2C=CC(F)=CC=2)=O)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]([NH:15]CCN2CCOCC2)C=1.[CH2:38]([O:45][C:46]1[CH:52]=[CH:51][C:49]([NH2:50])=[CH:48][CH:47]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.COCCOCCOC>O>[CH2:38]([O:45][C:46]1[CH:47]=[CH:48][C:49]([NH:50][C:13]2[N:12]=[CH:11][N:15]=[C:9]([O:8][C:7]3[CH:6]=[CH:5][C:4]([NH:24][C:25](=[O:37])[CH3:26])=[CH:3][C:2]=3[F:1])[CH:14]=2)=[CH:51][CH:52]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of N-(4-(6-chloropyrimidin-4-yloxy)-3-fluorophenyl)acetamide (Compound B of Example 13, 281 mg, 1.00 mmol), 4-benzyloxyaniline (Aldrich, 398 mg, 2.00 mmol), and 2-methoxyethyl ether (2 mL) was heated at 160° C. for 45 min. The cooled mixture was treated with H2O (50 mL) and extracted with EtOAc (100 mL). The EtOAc extract was washed with brine (3×25 mL), dried (MgSO4) and concentrated in vacuo to give the title compound (200 mg, 22%) as a purple solid. 1H NMR (400 MHz, DMSO-d6) δ 10.19 (s, 1H), 9.43 (s, 1H), 8.23 (s, 1H), 7.72 (dd, 1H, J=12.5, 2.0 Hz), 7.44-7.42 (m, 4H), 7.38 (dd, 2H, J=8.0, 6.9 Hz), 7.33-7.23 (m, 3H), 6.98 (d, 2H, J=9.0 Hz), 6.07 (s, 1H), 5.07 (s, 2H), 2.05 (s, 3H); MS (ESI+) m/z 445.13 (M+H)+.

Workup

extractionextracted with EtOAc (100 mL)
extractionThe EtOAc extract
washwas washed with brine (3×25 mL)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-a3071a6da2b24e7da01db3c588eca107
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989477B2

Reaction notes

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