Pyridine → HCID 69558262, compound

HRID 1934436Notes

Reaction equation

HRID 1934436 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][O:5][C:6]1[C:7]2[CH:14]=[C:13]([CH2:15][CH3:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[C:8]=2[N:9]=[CH:10][N:11]=1.[C:26](Cl)(=[O:30])[C:27](Cl)=[O:28].[N:32]1C=CC=CC=1>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:25])[CH2:4][O:5][C:6]1[C:7]2[C:14]([C:26](=[O:30])[C:27]([NH2:32])=[O:28])=[C:13]([CH2:15][CH3:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=3)[C:8]=2[N:9]=[CH:10][N:11]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 65578Oxalyl chloride2×HCID 69557385HCID 69557385, compound

Product 1

HCID 69558262HCID 69558262, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a suspension of 140 mg (0.407 mmol) of [[6-ethyl-7-[(3-fluorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester in 5 mL of chloroform was added 0.053 mL of oxalyl chloride followed by 0.10 mL of pyridine. The reaction was stirred for 30 hours at ambient temperature then an additional 0.10 mL of oxalyl chloride was added. This mixture was stirred and additional 2 days then quenched into 4.0 mL of dilute ammonium hydroxide. The product was extracted into 4.0 mL of methylene chloride. The organic phase was washed with saturated sodium chloride, dried with sodium sulfate and concentrated to 300 mg of crude oil. The residue was purified by flash chromatography (30 g of silica, hexanes-ethyl acetate gradient 100:0 to 25:75) to provide 28 mg (17%) of [[5-(aminooxoacetyl)-6-ethyl-7-[(3-fluorophenyl)methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as a solid. nmr (300 MHz, CDCl3) δ1.20 (t, 3H), 2.88 (q, 2H), 3.70 (s, 3H), 4.98 (s, 2H), 5.44 (s, 2H), 6.00 (s, 1H), 6.60 (s, 1H), 6.84 (m, 2H), 6.90 (dt, 1H), 7.20 (dt, 1H), 8.39 (s, 1H)

Workup

  1. stirringThis mixture was stirred and additional 2 days
  2. customthen quenched into 4.0 mL of dilute ammonium hydroxide
  3. extractionThe product was extracted into 4.0 mL of methylene chloride
  4. washThe organic phase was washed with saturated sodium chloride
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated to 300 mg of crude oil
  7. customThe residue was purified by flash chromatography (30 g of silica, hexanes-ethyl acetate gradient 100:0 to 25:75)

Sources & evidence

ORD record
ord-1f2da5fc62f442769ac51e4118523b2d
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

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