Hydrochloric Acid → HCID 72191836, compound

HRID 531272Notes

Reaction equation

HRID 531272 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[C:11]([CH2:20][N:21]3[C@@H:25]([CH3:26])[C@@H:24]([C:27]4[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=4)[O:23][C:22]3=[O:35])=[N:12][C:13](S(C)(=O)=O)=[N:14][CH:15]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.Cl.[F:37][CH:38]1[CH2:41][NH:40][CH2:39]1.CCN(CC)CC.Cl>C1COCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2[C:11]([CH2:20][N:21]3[C@@H:25]([CH3:26])[C@@H:24]([C:27]4[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=4)[O:23][C:22]3=[O:35])=[N:12][C:13]([N:40]3[CH2:41][CH:38]([F:37])[CH2:39]3)=[N:14][CH:15]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 101250543-fluoroazetidine HydrochlorideHCID 118021311HCID 118021311, compound

Product 1

HCID 72191836HCID 72191836, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

(4S,5R)-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-5-(3,5-difluorophenyl)-4-methyl-1,3-oxazolidin-2-one (Step A, 519 mg, 0.989 mmol) and 3-fluoroazetidine hydrochloride (331 mg, 2.97 mmol) were placed in a microwave vial and suspended in THF (3 mL). Et3N (0.689 mL, 4.94 mmol) was added, the vial was sealed and the reaction heated to 100° C. for 20 minutes in a microwave reactor. LCMS showed complete conversion to product. The reaction was diluted with ethyl acetate (50 mL) and poured into 0.1N HCl solution (50 mL). The ethyl acetate layer was washed with brine (50 mL), dried over sodium sulfate and concentrated on rotary evaporator. Silica gel purification employing a 0-50% ethyl acetate/hexanes linear gradient followed by isocratic elution at 50% ethyl acetate/hexanes gave the product as a pale yellow solid. LCMS (M+H)+: 520.3. 1H NMR (500 MHz, CDCl3): δ 8.19 (d, J=2.5 Hz, 1H), 8.14 (s, 1H), 7.48 (d, J=2.5 Hz, 1H), 6.84 (m, 3H), 5.52 (m, 1.5H), 5.42 (m, 0.5H), 4.64 (d, J=17.3 Hz, 1H), 4.49 (m, 2H), 4.35 (m, 2H), 3.98 (d, J=17.3 Hz, 1H), 4.07 (m, 4H), 3.95 (s, 3H), 0.78 (d, J=6.6 Hz, 3H). SPA IC50: 728 nM.

Workup

  1. customthe vial was sealed
  2. washThe ethyl acetate layer was washed with brine (50 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated on rotary evaporator
  5. customSilica gel purification
  6. washlinear gradient followed by isocratic elution at 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-30d8dcf573d84fcdbfb9e6b1fd8bb7e9
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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