4-Methylmorpholine → HCID 22050163, compound

HRID 1832126Notes

Reaction equation

HRID 1832126 reaction equation
[Br:1][C:2]1[C:3](=[O:28])[N:4]([CH2:19][C:20]2[O:24][C:23]([C:25](O)=[O:26])=[CH:22][CH:21]=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:31]=1.CN1CCOCC1.[OH-].[NH4+]>C1COCC1.[Cl-].[Na+].O>[Br:1][C:2]1[C:3](=[O:28])[N:4]([CH2:19][C:20]2[O:24][C:23]([C:25]([NH2:31])=[O:26])=[CH:22][CH:21]=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 22050159HCID 22050159, compound

Product 1

HCID 22050163HCID 22050163, compoundYield 74,214.102%

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]methyl}-2-furoic acid (500 mg, 1.10 mmol) in THF (6.0 mL) was added 2-chloro-4,6 dimethoxy-1,3,5 triazine (307 mg, 1.75 mmol) and N-methyl morpholine (NMM, 184 mg, 1.82 mmol) sequentially. The resulting solution was matured for 2 hours and then a saturated aqueous solution of ammonium hydroxide (0.70 mL) was added. The resulting suspension was allowed to continue for 1 additional hour. The reaction mixture was diluted with 400 mL of brine and extracted with ethyl acetate (3×400 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 (370 g, 74%). 1H NMR (300 MHz, d4-MeOH) δ 7.64 (app q, J=8.1 Hz, 1H), 7.10-7.00 (m, 3H), 6.53 (s, 1H), 6.52 (d, J=3.4 Hz, 1H), 5.43 (s, 2H), 5.32 (s, 2H), 2.61 (s, 3H); LC/MS C-18 column, tr=2.15 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 453 (M+H). ES-HRMS m/z 453.0249 (M+H calcd for C19H16BrF2N2O4 requires 453.0256).

Workup

  1. extractionextracted with ethyl acetate (3×400 mL)
  2. customThe organic extracts were separated
  3. dry with materialNa2SO4 dried
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-aff28e5ae5bb4d12ab90e9fe90e95c45
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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