Pyridine → HCID 22050895, compound

HRID 1867159Notes

Reaction equation

HRID 1867159 reaction equation
[Br:1][C:2]1[C:3](=[O:31])[N:4]([C:20]2[CH:21]=[C:22]([CH:27]=[CH:28][C:29]=2[CH3:30])[C:23]([NH:25][CH3:26])=[O:24])[C:5]([CH2:18][OH:19])=[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].N1C=CC=CC=1.[C:38](OC(=O)C)(=[O:40])[CH3:39]>>[C:38]([O:19][CH2:18][C:5]1[N:4]([C:20]2[CH:21]=[C:22]([C:23]([NH:25][CH3:26])=[O:24])[CH:27]=[CH:28][C:29]=2[CH3:30])[C:3](=[O:31])[C:2]([Br:1])=[C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[CH:6]=1)(=[O:40])[CH3:39]

Participants

4

Reactant 3

HCID 1049Pyridine2×HCID 7918Acetic Anhydride2×HCID 22050534HCID 22050534, compound

Product 1

HCID 22050895HCID 22050895, compoundYield 61%

Procedure

To a solution of 3-[3-bromo-4-[(2,4-difluorobenzyl)oxy]-6-(hydroxymethyl)-2-oxopyridin-1(2H)-yl]-N,4-dimethylbenzamide, (225 mg, 0.50 mmol) stirred in CH12Cl2 was added pyridine (55 μL, 0.69 mmol). To the resulting homogeneous solution was then added acetic anhydride (47 μL, 0.51 mmol). The mixture was stirred at rt for 3 h. Additional pyridine (150 μL, 1.8 mmol) and acetic anhydride (100 μL, 1.05 mmol) were then added and the reaction was allowed to stir overnight at rt. The reaction was then quenched with 1N NHCl4 and diluted with CH2Cl2. The layers were separated and the organic layer was then extracted with CH2Cl2 (3×). The organics were then combined, dried, and concentrated in vacuo. The residue was then triturated with Et2O and filtered to give (150 mg, 61%) an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.48 (br s, 1H), 7.87 (app d, J=7.8 Hz, 1H), 7.74-7.69 (m, 2H), 7.52 (d, J=7.5 Hz, 1H), 7.40 (app t, J=8.1 Hz, 1H), 7.28-7.19 (m, 1H), 6.91 (s, 1H), 5.43 (s, 2H), 4.60 (s, 2H), 2.79 (s, 3H), 2.06 (s, 3H), 1.94 (s, 3H). ES-HRMS m/z 535.0676 (M+H calcd for C24H22N2F2BrO5 requires 535.0675).

Workup

  1. stirringto stir overnight at rt
  2. customThe reaction was then quenched with 1N NHCl4
  3. additiondiluted with CH2Cl2
  4. customThe layers were separated
  5. extractionthe organic layer was then extracted with CH2Cl2 (3×)
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe residue was then triturated with Et2O
  9. filtrationfiltered

Sources & evidence

ORD record
ord-917c6f65850a489b91723072159be132
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

Loading…