Dimethylformamide → HCID 21345162, compound

HRID 367083Notes

Reaction equation

[F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([F:9])[N:3]=1.S([C:14]1[CH:20]=[CH:19][C:17](C)=[CH:16][CH:15]=1)(O)(=O)=O.FC1N=CC(O[CH2:29][C@@H:30]2[CH2:33][CH2:32][N:31]2[CH3:34])=CC=1.[OH-:35].[K+].CN([CH:40]=[O:41])C>[Cl-].[Na+].O>[F:1][C:2]1[C:7]([O:8][CH2:29][C@@H:30]2[CH2:33][CH2:32][N:31]2[C:34]([O:41][CH2:40][C:14]2[CH:20]=[CH:19][CH:17]=[CH:16][CH:15]=2)=[O:35])=[CH:6][CH:5]=[C:4]([F:9])[N:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

2,6-DiFluoro-3-hydroxypyridine from Example 116a (2g, 15.26 mmole), 1-Cbz-2-(S)-azetidinemethyl tosylate (5.73 g 15.26 mmole, prepared in example 105), and KOH (1.4 g 24.9 mmole) were combined in DMF (15 mL) and heated at 90° C. for one hour, cooled to 20° C. and poured into brine (100 mL). The resulting mixture was extracted with ether. The combined Et2O extracts were washed with 50% brine and dried (MgSO4). The solvent was evaporated in vacuo and the crude product was chromatographed (silica gel; hexane/EtOAc 95:5 to 6:4) to yield 1.75g (34%) of the title compound. 1H NMR (DMSO-d6, 120° C. 300 MHz) δ: 2.22 (m, 1H), 2.42 (m, 1H), 3.85-3.90 (m, 2H), 4.23 (m, 1H), 4.40 (m, 1H), 4.54 (m, 1H), 5.01 (s, 1H), 6.93 (dd, J=3.0, 5.5, 1H), 7.29 (m, 5H), 7.77 (m, 1H).MS (DCI/NH3) m/e 335 (M+H)+, 352 (M+NH4)+. Anal. calcd. for C17H16F2N2O3,: C 61.07 H, 54.82 N, 8.38 Found: C, 61.10 H, 4.84; N, 7.90.

Workup

temperaturecooled to 20° C.
extractionThe resulting mixture was extracted with ether
washThe combined Et2O extracts were washed with 50% brine
dry with materialdried (MgSO4)
customThe solvent was evaporated in vacuo
customthe crude product was chromatographed (silica gel; hexane/EtOAc 95:5 to 6:4)

Sources & evidence

ORD record: ord-d3ce365dfcb145eba05274b6c5337f54
Source dataset: uspto-grants-2000_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06133253

Reaction notes

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