Triethylamine → HCID 86666562, compound

HRID 2088869Notes

Reaction equation

HRID 2088869 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH2:8])[C:3]=1[CH2:9][NH:10][CH2:11][C:12]([F:15])([F:14])[F:13].C(N(CC)CC)C.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][C:24](=[O:26])[N:10]([CH2:11][C:12]([F:14])([F:15])[F:13])[CH2:9][C:3]=12

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 86666563HCID 86666563, compound

Product 1

HCID 86666562HCID 86666562, compoundYield 42.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Combine 6-chloro-5-((2,2,2-trifluoroethylamino)methyl)pyrimidin-4-amine (9.57 g, 39.78 mmol), triethylamine (5.50 mL, 2.0 eq), and dichloromethane (795 mL). Cool to 0° C. under nitrogen. Add a solution of triphosgene (11.85 g, 1.0 eq) in dichloromethane (228 mL). Stir at 0° C. for 30 min, and allow to warm to room temperature. Heat the reaction mixture to 40° C. overnight. Add aqueous sodium bicarbonate and extract with ethyl acetate. Dry the organics over anhydrous sodium sulfate, filter, and concentrate in vacuo. Purify by silica gel chromatography, eluting with 9:1 dichloromethane:methanol, to give the title compound (4.50 g, 42%). 1H NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H), 8.41 (s, 1H), 4.20 (m, 2H), 3.25 (s, 2H).

Workup

  1. temperatureto warm to room temperature
  2. temperatureHeat the reaction mixture to 40° C. overnight
  3. extractionAdd aqueous sodium bicarbonate and extract with ethyl acetate
  4. dry with materialDry the organics over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by silica gel chromatography
  8. washeluting with 9:1 dichloromethane

Sources & evidence

ORD record
ord-b08b39218ecf4ccc931fb7bbc219822e
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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