4-Methylmorpholine → HCID 22049901, compound

HRID 1832128Notes

Reaction equation

HRID 1832128 reaction equation
[Br:1][C:2]1[C:3](=[O:27])[N:4]([C:19]2[O:23][C:22]([C:24](O)=[O:25])=[CH:21][CH:20]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].ClC1N=C(OC)N=C(OC)[N:30]=1.CN1CCOCC1.[OH-].[NH4+]>C1COCC1.[Cl-].[Na+].O>[Br:1][C:2]1[C:3](=[O:27])[N:4]([C:19]2[O:23][C:22]([C:24]([NH2:30])=[O:25])=[CH:21][CH:20]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 14923Ammonium HydroxideHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 22050576HCID 22050576, compound

Product 1

HCID 22049901HCID 22049901, compoundYield 71.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a room temperature suspension of 5-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]-2-furoic acid (1.00 g, 2.27 mmol) in THF (8.0 mL) was added 2-chloro-4,6 dimethoxy-1,3,5 triazine (610 mg, 3.47 mmol) and N-methyl morpholine (NMM, 368 mg, 3.62 mmol) sequentially. The resulting solution was matured for 2 hours and then a saturated aqueous solution of ammonium hydroxide (1.5 mL) was added. The resulting suspension was allowed to continue for 1 additional hour. The reaction mixture was diluted with 800 mL of brine and extracted with ethyl acetate (3×600 mL). The organic extracts were separated, Na2SO4 dried, and concentrated in vacuo and the resulting residue was subjected to SiO2 chromatography with ethyl acetate/hexanes/methanol (57:38:5) to provide the title compound (710 mg, 71%). 1H NMR (400 MHz, d7-DMF) δ 8.07 (s, 1H), 7.79 (app q, J=8.6 Hz, 1H), 7.50 (br s, 1H), 7.32 (app dt, J=10.1, 2.2 Hz, 1H), 7.30 (app dd, J=8.0, 3.3 Hz, 1H), 7.20 (app dt, J=8.6, 2.0 Hz, 1H), 6.81 (s, 1H), 6.79 (d, J=3.4 Hz, 1H), 5.47 (s, 2H), 2.14 (s, 3H); LC/MS C-18 column, tr=2.60 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 439 (M+H). ES-HRMS m/z 439.0088 (M+H calcd for C18H14BrF2N2O4 requires 439.0010).

Workup

  1. extractionextracted with ethyl acetate (3×600 mL)
  2. customThe organic extracts were separated
  3. dry with materialNa2SO4 dried
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d771fb57e49844e2b76845242723326f
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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