Pyridine → HCID 69558357, compound

HRID 1934455Notes

Reaction equation

HRID 1934455 reaction equation
[CH3:1][O:2][C:3](=[O:28])[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]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:8]=2[N:9]=[CH:10][N:11]=1.[C:29](Cl)(=[O:33])[C:30](Cl)=[O:31].[N:35]1C=CC=CC=1>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][C:6]1[C:7]2[C:14]([C:29](=[O:33])[C:30]([NH2:35])=[O:31])=[C:13]([CH2:15][CH3:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:26])([F:25])[F:27])[CH:19]=3)[C:8]=2[N:9]=[CH:10][N:11]=1

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 65578Oxalyl chloride2×HCID 69558333HCID 69558333, compound

Product 1

HCID 69558357HCID 69558357, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a suspension of 115 mg (0.29 mmol) of [[6-ethyl-7-[[3-(trifluoromethyl)phenyl]methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester in 3 mL of chloroform was added 0.102 mL of oxalyl chloride followed by 0.094 mL of pyridine. The reaction was stirred for 48 hours at ambient temperature then an additional 0.100 mL of oxalyl chloride and 0.100 mL of pyridine was added. This mixture was stirred and additional 4 days then quenched into solution prepared from 4 mL of water and 2 mL of concentrated ammonium hydroxide. The mixture was partitioned by the addition of 20 mL of ethyl acetate and 10 mL of water. The organic phase was dried with sodium sulfate and concentrated to 108 mg of crude solid. The residue was purified by flash chromatography (7 g of silica, ethyl acetate) to provide 72 mg (53%) of [[5-(aminooxoacetyl)-6-ethyl-7-[[3-(trifluoromethyl)phenyl]-methyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]acetic acid methyl ester as a white solid. nmr (500 MHz, CDCl3) δ1.15 (t, J=7.5 Hz, 3H), 2.96 (q, J=7.5 Hz, 2H), 3.78 (s, 3H), 5.07 (s, 2H), 5.57 (s, 2H), 5.68 (br s, 1H), 6.60 (br s, 1H), 7.24 (d, J=7.8 Hz, 1H), 7.40 (d, J=7.8 Hz, 1H), 7.54 (s, 1H), 7.55 (d, J=7.8 Hz, 1H), 8.46 (s, 1H)

Workup

  1. stirringThis mixture was stirred and additional 4 days
  2. customthen quenched into solution
  3. customprepared from 4 mL of water and 2 mL of concentrated ammonium hydroxide
  4. customThe mixture was partitioned by the addition of 20 mL of ethyl acetate and 10 mL of water
  5. dry with materialThe organic phase was dried with sodium sulfate
  6. concentrationconcentrated to 108 mg of crude solid
  7. customThe residue was purified by flash chromatography (7 g of silica, ethyl acetate)

Sources & evidence

ORD record
ord-533953d9e60f4193806e956ce5246086
Source dataset
uspto-grants-2002_05
Patent number
US06384041B1

Reaction notes

Loading…