Oxalyl chloride → HCID 73775924, compound

HRID 2199413Notes

Reaction equation

HRID 2199413 reaction equation
[F: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.[C:34]([NH:38][CH2:39][CH3:40])([CH3:37])([CH3:36])[CH3:35]>ClCCl.CN(C=O)C.C1COCC1>[C:34]([N:38]([CH2:39][CH3:40])[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]([F:1])[CH:3]=2)=[CH:11][N:12]=1)=[O:18])([CH3:37])([CH3:36])[CH3:35]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 521156N-tert-ButylethylamineHCID 90103363HCID 90103363, compound

Product 1

HCID 73775924HCID 73775924, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(100 mg, 0.41 mmol) 5-(3-Fluoro-phenylethynyl)-pyrimidine-2-carboxylic acid (Example 3, step 1) was suspended in dichloromethane (1 ml) and DMF (10 μl). Oxalyl chloride (40 μl, 0.45 mmol, 1.1 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 tert-butylethylamine (43 mg, 0.41 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 5-(3-fluoro-phenylethynyl)-pyrimidine-2-carboxylic acid tert-butyl-ethyl-amide (97 mg, 78% yield) was obtained as a white solid, MS: m/e=326.5 (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-8c90cb8d2dd5473b89e2fb5b90bc91e6
Source dataset
uspto-grants-2016_06
Patent number
US09359301B2

Reaction notes

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