Dimethylformamide → HCID 21345174, compound

HRID 367087Notes

Reaction equation

[F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([CH3:9])[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]([CH3:9])[N:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

2-Fluoro-3-hydroxy-6-methylpyridine from Example 117c (1 g 7.87 mmole), 1-Cbz-2-(S)-azetidinemethyl tosylate (2.37 g 7.5 mmole, prepared as for example 105) and KOH (0.66 g 11.76 mmole) were combined in DMF (25 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 under vacuum, and the crude product was chromatographed (silica gel; hexane/EtOAc 3:1) to yield 1.31 g (53%) of the title compound. 1H NMR (DMSO-d6, 120° C. 300 MHz) δ: 2.26 (m, 1H), 2.33 (s, 3H), 2.48 (m, 1H), 3.82-3.88 (m, 2H), 4.19 (q, J=3, 1H), 4.35 (q, J=4.5, 1H), 4.53 (m, 1H), 5.01 (s, 211), 7.01 (d, J=8, 1H), 7.28 (m, 5H), 7.43 (m, 1H). MS (DCI/NH3) m/e 331 (M+H)+, 348 (M+NH4)+. Anal. calcd. for C18H19FN2O3C, 65.44; H, 5.8; N, 8.48. Found: C, 65.04 H, 5.86; N, 8.44; [α]D -70.38 (c 1, MeOH).

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 under vacuum
customthe crude product was chromatographed (silica gel; hexane/EtOAc 3:1)

Sources & evidence

ORD record: ord-36324c6d0c2b4e9db9259d256d2ea235
Source dataset: uspto-grants-2000_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06133253

Reaction notes

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