Oxalyl chloride → HCID 73775704, compound

HRID 588077Notes

Reaction equation

HRID 588077 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:11]=[N:12][C:13]([C:16]([OH:18])=O)=[N:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[CH3:34][C:35]1([CH3:41])[CH2:40][O:39][CH2:38][CH2:37][NH:36]1>ClCCl.CN(C=O)C.C1COCC1>[CH3:34][C:35]1([CH3:41])[CH2:40][O:39][CH2:38][CH2:37][N:36]1[C:16]([C:13]1[N:14]=[CH:15][C:10]([C:9]#[C:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)=[CH:11][N:12]=1)=[O:18]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 145518493,3-DimethylmorpholineHCID 90102723HCID 90102723, compound

Product 1

HCID 73775704HCID 73775704, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(100 mg, 0.39 mmol) 5-(3-Chloro-phenylethynyl)-pyrimidine-2-carboxylic acid (Example 4, step 1) was suspended in dichloromethane (1 ml) and DMF (10 μl). Oxalyl chloride (51 μl, 0.59 mmol, 1.5 equiv.) was added drop wise at room temperature and the mixture was stirred for 1 hour at reflux. The reaction mixture was then added to a mixture of diisopropylethylamine (235 μl, 1.34 mmol, 3.3 equiv.) and 3,3-dimethylmorpholine (46 mg, 0.40 mmol, 1 equiv.) in THF (2 ml). The mixture was stirred for 16 hours at room temperature and evaporated in presence of Isolute® sorbent to dryness. The crude product was purified by flash chromatography with a 20 g silica gel column eluting with heptane:ethyl acetate 100:0→0:100. The desired (3,3-dimethyl-morpholin-4-yl)[5-(3-chloro-phenylethynyl)-pyrimidin-2-yl]-methanone (120 mg, 94% yield) was obtained as a white solid, MS: m/e=356.6/358.6 (M+H+).

Workup

  1. temperatureat reflux
  2. stirringThe mixture was stirred for 16 hours at room temperature
  3. customevaporated in presence of Isolute® sorbent to dryness
  4. customThe crude product was purified by flash chromatography with a 20 g silica gel column
  5. washeluting with heptane:ethyl acetate 100:0→0:100

Sources & evidence

ORD record
ord-d615c107fa6247f0bf29bfa1bbcd4623
Source dataset
uspto-grants-2016_01
Patent number
US09227959B2

Reaction notes

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